2018 PHYS REV Ingestão Alimentar e Comportamento Alimentar Depois de Cirurgia Bariátrica

Physiol Rev 98: 1113–1141, 2018
Published May 2, 2018; doi:10.1152/physrev.00021.2017
FOOD INTAKE AND EATING BEHAVIOR AFTER

BARIATRIC SURGERY
Werd Al-Najim, Neil G. Docherty, and X Carel W. le Roux
Diabetes Complications Research Centre, Conway Institute, School of Medicine and Medical Sciences, University
College Dublin, Dublin, Ireland; Department of Gastrosurgical Research and Education, Institute of Clinical
Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; and Investigative Science,
Imperial College London, London, United Kingdom
Al-Najim W, Docherty NG, le Roux CW. Food Intake and Eating Behavior After
L
Bariatric Surgery. Physiol Rev 98: 1113–1141, 2018. Published May 2, 2018;
doi:10.1152/physrev.00021.2017.—Obesity is an escalating global chronic disease.
Bariatric surgery is a very efficacious treatment for obesity and its comorbidities.
Alterations to gastrointestinal anatomy during bariatric surgery result in neurological
and physiological changes affecting hypothalamic signaling, gut hormones, bile acids, and gut
microbiota, which coalesce to exert a profound influence on eating behavior. A thorough under-
standing of the mechanisms underlying eating behavior is essential in the management of patients
after bariatric surgery. Studies investigating candidate mechanisms have expanded dramatically in
the last decade. Herein we review the proposed mechanisms governing changes in eating behavior,
food intake, and body weight after bariatric surgery. Additive or synergistic effects of both condi-
tioned and unconditioned factors likely account for the complete picture of changes in eating
behavior. Considered application of strategies designed to support the underlying principles gov-
erning changes in eating behavior holds promise as a means of optimizing responses to surgery
and long-term outcomes.
I. IMPORTANT TERMS 1113 beginning with hunger and proceeding through satiation
II. INTRODUCTION 1113 and satiety, before returning to hunger (85). The conse-
III. OBESITY AND BARIATRIC SURGERY 1113 quences of when this loop becomes pathological are either
IV. BIOPSYCHOLOGY OF HUNGER,... 1116 overweight or underweight. Obesity and its associated com-
V. EATING BEHAVIOR AFTER... 1117 plications are increasing unabated, but bariatric surgery is
VI. MECHANISMS OF CHANGED... 1121 an effective treatment (50, 194, 254).
VII. CONCLUSION AND PERSPECTIVES 1132
Over the past decade, our knowledge of eating behavior has
increased dramatically, in particular the molecular and an-
I. IMPORTANT TERMS atomical basis of satiety. Important advances in the charac-
terization of the processes involved in eating behavior and
Hunger is the motivational impulse to seek and consume the changes that occur following bariatric surgery have oc-
food, geared towards initiating an eating episode. curred. More complete understanding of the changes in
eating behavior after surgery may help in the design of
Satiation is the process that brings an eating episode to an strategies to optimize the outcomes of bariatric surgery and
end. It commences when the gut senses fullness or when the moreover aid discovery of nonsurgical interventions for
person is satisfied with the amount consumed. weight loss and weight loss maintenance.
Satiety is the state in which the hunger drive, and conse-

quently eating episode, is inhibited. III. OBESITY AND BARIATRIC SURGERY
Obesity has been declared a chronic disease by a number of

II. INTRODUCTION global health organizations including the World Health Or-
ganization (WHO), Food and Drug Administration (FDA),
Hunger and satiation are the predominant signals involved the National Institutes of Health (NIH), the American Med-
in the initiation or termination of a meal. Psychological ical Association (AMA), and the Canadian Medical Associ-
experiences, peripheral physiological signals, and central ation (CMA) (6, 60). Worldwide the rates of obesity have
neural processes interact before, during, and after food in- reached epidemic proportions bringing with it a burden of
take to form a biopsychological closed loop conceptually associated comorbidities and negative impact on quality of
0031-9333/18 Copyright © 2018 the American Physiological Society 1113

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AL-NAJIM ET AL.
life. Obesity likely represents a common phenotypic presen- larly gastric bypass and sleeve gastrectomy to more ac-
tation of several complex disorders involving maladaptive curately capture the breadth of physiological changes
changes in eating behavior, appetite regulation, and energy induced. Moreover, advocates of this alternative termi-
metabolism. Therefore, prevention and management of nology also point to the shift in emphasis it provides
obesity requires a multifaceted approach to achieve realistic towards viewing the health benefits associated with
goals. weight loss rather than simply weight loss itself as being
the key outcome (250).
Lifestyle changes together with diet and exercise are usually
considered as the first lines of prophylaxis and therapy in The Roux-en-Y gastric bypass (RYGB) is the procedure
weight management treatments and are the mainstay of most commonly and consistently performed over the last
associated public health messages. This is not dissimilar to three decades due to its effectiveness in weight loss and
lifestyle changes being the cornerstone of the public health weight loss maintenance (35). Nevertheless, RYGB is a
message in relation to the prevention and management of
technically demanding procedure and is associated with
hypertension, dyslipidemia, or diabetes. Frustratingly how-
major rearrangement of the normal gastrointestinal anat-
ever, lifestyle approaches for obesity are of limited efficacy
omy. In this procedure, the stomach is transected to gener-
in managing and treating severe overweight and its comor-
ate a small gastric pouch 15⫺30 ml in volume, and a lower
bidities. This is disappointing to clinicians and patients as
larger gastric remnant excluded from contact with food.
many fail to maintain weight loss in the long term. Only
around 15% of obese and overweight people who attempt The gastric pouch is then anastomosed to the distal limb of
to lose excess weight by diet therapy can manage to sustain a jejunotomy performed at the mid-jejunum thus forming
10% weight loss over a period of 1 yr (160). Dietary-in- the alimentary or Roux limb. In the absence of gastric res-
duced weight loss tends to be largely unsustainable with ervoir function or sphincter control, this rearrangement al-
weight rebound within 1 yr. In the majority of cases, all lows essentially instantaneous transfer of ingested food to
weight lost is regained within 3–5 yr (321). the small intestinal lumen. Gastric, pancreatic, and biliary
secretions flow undiluted in the biliopancreatic limb proxi-
In contrast to dietary approaches, bariatric surgery is a mal to the jejunal transection and are permitted to mix with
highly successful intervention for the treatment of obesity chyme in a common channel formed by side-to-side anas-
and diabetes and is becoming increasingly popular due to its tomosis of the biliopancreatic limb 100 –150 cm distal to
ability to foster substantial and sustainable weight loss with the gastro-jejunal anastomosis (218).
attendant improvements in health, functioning, and quality
of life (194, 211, 252, 254, 277). The Gastric Band (BAND) was previously more widely per-
formed but has declined in popularity in the last 5 yr (35).
This procedure involves the insertion of an adjustable hol-
A. Surgical Modalities low plastic and silicone ring around the stomach just below
the gastric cardia, creating a small pouch and a narrow
Bariatric surgery is an option for those obese patients for passage to the remaining part of the stomach. This proce-
whom lifestyle- and medication-based approaches have dure was originally thought to physically restrict meal size
proven ineffective. Bariatric surgery procedures have evolved and delay emptying of food from the pouch, thus producing
over the years starting from radical small bowel operations early and prolonged satiety (20). However, much of the
such as the jejunal-ileal bypass in the 1950s, to the gastric
effect of the procedure is now thought to be provoked by
bypass in the late 1960s (4, 120, 183), gastric banding in the
pressure applied on the Intraganglionic Laminar Endings
1990s (162), and the more recently popularized vertical sleeve
(IGLES) which relay afferent signals resulting in reductions
gastrectomy (5). Refinements to lessen the extent of recon-
in hunger (286). The gastric BAND causes a delayed bolus
figuration alongside the routine use of laparoscopic ap-
proaches have made the procedures safer, more efficient, transit into the infraband stomach but does not change
and characterized by a less severe side-effect profile (106). overall gastric emptying half-time, a key observation in re-
Under certain circumstances, more radical procedures like lation to the differential effect of BAND versus RYGB on
the Biliopancreatic Diversion/Duodenal Switch (BPD/DS) satiety, a topic developed in detail later in this manuscript
may still be used on occasion for cases of severe obesity with (41). Vertical Sleeve Gastrectomy (VSG) has become in-
significant complications, though the procedure is less pop- creasingly popular due to its relative simplicity and good
ular due to the high burden of postoperative nutritional clinical outcomes (46). VSG involves the excision of 70 –
deficiencies and related complications (10). 80% of the stomach to make a small stomach that creates a
high-pressure chamber that easily generates pressures suffi-
The different bariatric procedures currently vary with re- cient to overcome pyloric sphincter tone and thus results in
gard to their relative metabolic benefits, as well as surgical rapid gastric emptying.
risks. In some quarters, the term metabolic surgery is now
preferred to describe certain types of surgeries particu- FIGURE 1 shows the different bariatrics procedures.
1114 Physiol Rev • VOL 98 • JULY 2018 • www.prv.org

BARIATRIC SURGERY, FOOD INTAKE, AND BEHAVIOR
FIGURE 1. Anatomy of different bariatric procedures. Figures from left to right show RYGB, BAND, VSG, and
BPD/DS.
B. Positive and Negative Repercussions of to several possible organic diseases of the gastrointestinal
Surgical Weight Loss tract (119). Hypoglycemia occurs in 64 – 82% of patients
during the first 5 years of bariatric surgery (254). Several
Bariatric surgery produces 15–30% weight loss (1, 53, 139, hypotheses for its pathogenesis exist including improved B
145, 150, 214, 225, 226, 254, 275, 287), maintained for at cells mass and function, reduced level of ghrelin, improved
least 20 yr after procedures such as the RYGB. Moreover, insulin sensitivity, and failure of counterregulation (2).
glycemic control improves in 90% of patients after RYGB These complex side effects make it challenging for the treat-
(277). Short- and medium-term studies show that VSG is ing clinician and more importantly for the suffering patient
almost as effective as the RYGB with respect to short- to as they often persist in the long term and can thus cause
medium-term improvements in body weight loss and glyce- reduced quality of life.
mic control (1, 139, 145, 150, 225, 226, 254, 287). Bariat-
ric surgery also leads to improvement or remission of other Nutritional deficiencies occur in 30 –70% of patients after
obesity-related comorbidities such as hypertension, ob- bariatric surgery (123). Protein, iron, folate, calcium, and
structive sleep apnea, musculoskeletal pain, and overall vitamins B1, B12, and D are the most affected macro- and
quality of life (194, 211, 252, 254). micronutrients (14). Nutrient deficiency when severe can
lead to symptoms of edema, hypoalbuminemia, anemia,
Bariatric surgery does come with some unwanted conse- and hair loss (protein) as well as peripheral neuropathy
quences, making the decision to opt for this treatment a (folate, B12), Wernicke encephalopathy and beriberi (B1),
matter of the risks versus benefits on the balance for any metabolic bone disease (vitamin D, calcium), and anemia
particular individual. Around 4% of patients that undergo (iron) (14). Therefore, the quality of food consumed and
bariatric surgery have surgical complications within 30 nutritional monitoring are a critical part of the postsurgical
days of the operation, with the most common being bleed- management of patients. Lifelong multivitamin supplemen-
ing, perforation, or leakage (276). Later surgical complica- tation is also essential (232).
tions can also occur in 15–20% of patients; these include
small bowel obstruction, anastomotic stenosis, or marginal C. Set-Point Theory
ulceration (108). Both early and late surgical complications
can be diagnosed and treated with a surgical or endoscopic Despite the effectiveness of bariatric surgery as a means of
intervention. substantially reducing body weight over a relatively short
period of time, further weight loss to achieve the “ideal”
Medical complications can also occur after bariatric sur- body weight for aesthetic reasons often proves challenging.
gery and are sometimes more nuanced in terms of diagnosis The new stable body weight profile achieved by 12–18 mo
and treatment due to the complex and on occasion occult after bariatric surgery often appears to be “defended” with
nature of the etiology. Abdominal pain (particularly unex- the same vigor, as was the elevated body weight was before
plained abdominal pain) and hypoglycemic episodes in pa- bariatric surgery. Set-point defense theory is based on the
tients without diabetes are common and “not yet fully un- idea that body fat before and after bariatric surgery is main-
derstood” negative consequence. Abdominal pain is the tained through homeostatic systems around a “set point.”
main complaint of half of the emergency hospital admis- Certain schools of thought suggest that intrinsic adjust-
sions after RYGB (54). The pathogenesis varies widely from ments to food intake and energy expenditure can occur with
behavioral and nutritional disorders, functional disorders, the purpose of maintaining a genetically pre-engineered
Physiol Rev • VOL 98 • JULY 2018 • www.prv.org 1115

AL-NAJIM ET AL.
body fat set point in response to short-term fat gain or fat The peptide hormone releasing enteroendocrine cells in the
loss (44, 138, 171, 207, 238, 326). small intestine are classified according to a nomenclature
that differentiates between cell type according to discrete
A framework that incorporates this set-point theory is con- patterns of hormonal secretion. Recent evidence suggests
ceptually compelling as a means of understanding the con- that there is significant dynamic plasticity in the expression
sistent and resilient changes in body fat after bariatric sur- and release of enteroendocrine peptide hormones across the
gery as it implies that patients move to a new steady state recognized cell types. Plasticity permits adaptive changes in
characterized by a lower body fat set point. Many funda- hormone profile to occur as a function of dynamic change in
mental physiological questions still surround this theory. the surrounding environment, e.g., dietary nutrient compo-
What physiological parameter serves as the sensor to poten- sition, changes in relative anatomical position after surgery
tial deviations from set point, what structure(s) serves as the (127).
detector(s), and what system/systems are operative in de-
fending set point? Is set point really adjusted by bariatric
Cholecystokinin (CCK) is released from the I cells of the
surgery and could the process be mimicked nonsurgically?
upper intestinal enteroendocrine cells within minutes of
meal initiation (172). CCK was the first gut peptide estab-
All of these questions provide an ideal philosophical gate-
lished to have physiological relevance as an inhibitory sig-
way into the main topic of the present review, which seeks
nal to further food intake (114), and its role as a short-term
to delineate the role of changes in eating behavior as an
input into body fat set-point resetting after bariatric sur- meal-reducing signal has been extensively documented in
gery. mammalian species including humans (284).
Other prandial and postprandial signals are also generated

IV. BIOPSYCHOLOGY OF HUNGER, when nutrients are absorbed from the small intestine into
SATIATION, AND SATIETY the peripheral circulation. Those signals are vital in the
regulation of satiation and satiety processes. Insulin is re-
A useful first stop in the journey towards a comprehensive leased from the pancreas during the cephalic phase (pre-
description of what we know about changes to eating be- prandial) and peaks after the initiation of the meal to regu-
havior after bariatric surgery is a review of the biopsycho- late the absorption of glucose into the bloodstream. Glu-
logical framework of hunger and satiety. Hunger, the first cose is then carried to the brain to modulate the function of
phase of the satiety cascade, is defined as the urge to seek a variety of neurotransmitters and peptides associated with
and consume food, which triggers a feeding episode. The appetite regulation (135). The liver also plays a major role
behavior that terminates an eating episode is referred to as in metabolizing glucose, fatty acids, and amino acids (9).
satiation, whereas the process underpinning the transitional Hepatic energy metabolism generates satiety signals (9)
period between meals is referred to as satiety (30). transmitted from the liver to the central nervous system
(CNS) via the vagus nerve (135).
Hunger is driven by preprandial cognitive and sensory sig-
nals that promote food intake and prepare the body for A number of satiety peptides are released from the enteroen-
digestion (30). Preprandial signals are generated in part by docrine cells and peak after meal termination to sustain
hunger hormones such as ghrelin (69), hedonic stimulation satiety until the initiation of the next eating episode. Peptide
(the reward system), cognition and learned experiences
YY (PYY), glucagon-like peptide 1 (GLP-1), and oxynto-
(e.g., memory of last meal, meal times), and also by sensory
modulin (OXM) are released from the L cells in proportion
stimulation (e.g., sight and smell of food) (300). Once food
to the amount of calories consumed and meal composition
is present in the oral cavity, and during the early phase of an
(61, 74, 105). These hormones regulate short-term energy
eating episode, further hunger signals are generated by sen-
sory stimulation caused by the contact of food with taste balance. Leptin, on the other hand, is released from the
buds in the mouth (134). adipose tissues in proportion to body fat (179) and from the
gastric mucosa (281) to regulate long-term energy balance
During the meal (prandial phase), gastric distension caused (63). Similarly, insulin is also released in proportion to ad-
by the presence of food in the stomach is sensed by mecha- ipose tissues (229), and the brain interprets its levels to
noreceptors to detect the quantity eaten (188, 228) and adjust food intake accordingly (329).
signals are sent to the brain via the vagus nerve (23). When
chyme enters the small intestine, intestinal mechano- and It is important to highlight the fact that the short- and
chemoreceptors detect the quantity and quality of nutrients long-term signals modulate each other’s physiological func-
and send signals also via the vagus nerve to the nucleus tions. For instance, leptin stimulates GLP-1 secretion from
tractus solitarius (NTS) to alter the gastrointestinal motor, the L cells, and leptin resistance is associated with impaired
stimulate local peptide release, and activates vagal efferent secretion of GLP-1 (11). In addition, leptin may enhance the
fibers (182). CNS response to some gut hormones as suggested by Mor-

ton et al. (206). Many other hormonal interactions take and soft food for a further period before proceeding to
place, but they are beyond the scope of this review. “normal food.” By 3 mo, patients are encouraged to eat a
normal diet. Humans and animals are able to compensate
FIGURE 2 shows an integrated diagram of the biopsychology for smaller meal sizes after surgery by increasing meal fre-
of hunger, satiation, and satiety. quency (36, 163, 339). Despite the small size of the gastric
pouch in RYGB, there is usually little restriction as the
V. EATING BEHAVIOR AFTER BARIATRIC stoma between the gastric pouch and the small bowel is
SURGERY wide. High pressure manometry suggests normal pressures
in the esophagus, low pressures in the pouch, and higher
Clinicians ask patients after bariatric surgery to follow a pressures in the small bowel, indicating no restriction at the
staged progression diet consisting of a liquid diet for the level of the pouch (29). This allows food to progress from
first few days or weeks, pureed diet for several more weeks, the esophagus rapidly into the small bowel. The small
Cortex
Hypothalamic
Nuclei
Neuronal signals
NTS
gus
Va
STOP GO
CCK
Physiological signals
Ghrelin
Leptin Insulin
PYY
Metabolic demand
(Hunger) GLP-1
OXM
Psychological signals
Cognitive Oro-sensory
(sight, smell, texture)
Cognitive Pre-absorptive
Sensory Post-absorptive
Food
Early Late
Pre-prandial motivation Satiation Satiety
FIGURE 2. Biopsychology of hunger and satiety. Hunger, stimulated by cognitive or sensory factors, initiates
an eating episode, which in turn terminates when satiety is reached. During the meal, short-term energy
regulation signals including gut hormones are sent from the stomach and small intestine to the brain. Leptin
is secreted from the adipose tissues and insulin from the pancreas in proportion to body fat to regulate
long-term energy balance. All these signals are integrated in the brain to regulate food intake.

AL-NAJIM ET AL.
pouch does not cause restriction but rather may act as con- nism, and the body can no longer respond to elevated en-
duit to accelerate food into the small bowel. The small dogenous leptin levels. After weight loss, body fat reduces
bowel then requires adaptation to cope with the sudden and leptin levels decrease, initiating an anti-starvation
delivery of undigested food, and consequently gut adapta- mechanism with increased hunger. This hunger drive is part
tion may occur. of a homeostatic balance that tries to draw the body fat
back to its predieting set point or even higher, often raising
Patients after RYGB and sleeve gastrostomy sometimes re- the set point higher each dieting attempt (178).
port a shift away from consuming high-fat and high-sugar
products to healthier options. Despite reporting a reduced After bariatric surgery, patients describe having lower hun-
liking for foods like chocolates, sweets, and fried food, it ger levels and more postprandial fullness (165, 181, 204),
has remained unknown whether this reflects a conscious which leads to a significant negative energy balance and
avoidance based on advice, expectations, or assumed re- thus weight loss. However, energy balance stabilizes ~1 yr
sponsibility; changes in taste and palatability; conditioned after bariatric surgery (152, 200) but weight does not go
avoidance; conditioned aversion; or a change in food pref- back to the baseline levels (1, 53, 139, 145, 150, 214, 225,
erences due to an yet undefined other mechanism. 226, 254, 275, 287) and seems to be protected by a new
body fat set-point level (132) (FIGURE 3).
We speculate that immediate and short-term phases of food
intake after bariatric surgery are critical to the shaping of Verbal report using Visual Analogue Scales (VAS) is the
long-term changes in food intake and preferences in a sim- most common method of assessing hunger and fullness. le
ilar way to early infancy food exposure. Bariatric surgery Roux et al. (168) used VAS in patients after RYGB to assess
“resets” the set point of eating behavior in a similar manner changes in appetite in as early as 2 days postoperation.
to the set point for body fat. Ratings of hunger reduced to half while ratings of fullness
doubled. Both were maintained up to 42 days (75). This
A. Hunger and Fullness was consistent with other findings (48, 165, 204, 296). On
the other hand, Laurenius et al. (163) did not find a signif-
After a period of dieting and successful weight loss, the icant effect of RYGB surgery on the perception of hunger
subcortical areas of the brain, particularly the hypothala- before the meal, satiation after the meal, or maintained
mus and hindbrain (22, 149, 328), respond to weight loss satiety 1 h after a meal at any time point for up to 2 yr
with a compensation reaction consisting of “but not limited postoperation. However, in their study two different meal
to” increased hunger and reduced fullness signals (12, 51, sizes were used to accommodate the changes after sur-
71, 83, 84, 86, 294). Exogenous leptin given to rodents gery (163). Thus in the same study, when ad libitum meal
leads to reduced hunger levels and food intake. Leptin re- was assessed, RYGB patients had a significant reduction
sistance in obese people causes a disruption in this mecha- in meal size which resulted in the same level of satiety as
FIGURE 3. Influence of weight loss interventions on body fat set point. During a conventional diet therapy,
weight decreases during negative energy balance. When the diet is stopped, weight gradually increases and is
pulled back to the pre-diet set point or even higher, raising the set point during each dieting attempt. With
bariatric surgery, the set point is reset to be 20 –30% lower. Therefore, during stable energy balance, the
weight fluctuates around the “new” set point.

compared with presurgery (163), which supports the no- C. Frequency

tion that surgery results in the same level of satiation but
it only occurs with far fewer calories. Other studies also Bariatric procedures were originally designed to reduce the
confirmed similar levels of satiety using VAS post-RYGB size of the stomach in an attempt to cause restriction and
while subjects were losing weight (157), suggesting pa- induce weight loss, but most studies confirm that restriction
tients were not feeling deprived or hungry even while does not play a role in long-term weight loss maintenance.
they were losing weight secondary to being in a very steep Furnes et al. (112) suggested that the weight loss observed
negative energy balance. after VSG is independent of the food reservoir function of
the stomach. In addition, Wilson-Pérez et al. (325) hypoth-
Sleeve gastrectomy (SG) in some studies has been shown to esized that were VSG to result in reduced portion sizes due
reduce hunger and enhance postprandial fullness compara- to the reduced gastric size, then patients would develop a
ble to RYGB (312, 334). Differences between RYGB and compensatory adaptation by increasing fat intake to maxi-
BAND were assessed by Konor et al. (158) who demon- mise caloric intake. Wilson-Pérez et al. (325) used a rat
strated that RYGB produced higher levels of satiety at 3 h model of VSG and found that rats after VSG not only re-
post-meal ingestion as compared with BAND or subjects strict their food intake but also preferred less calorically
who were unoperated and overweight. dense foods. In addition, despite the markedly different sur-
gical manipulations, rats after VSG and RYGB had remark-
ably similar changes in food choices, i.e., less fat and more
B. Food Volume carbohydrates when compared with sham-operated rats
(325). This suggests a common underlying mechanism in
both procedures. Both procedures result in accelerated nu-
The first objectively quantifiable change after bariatric sur-
trient transfer to the small intestine, and this may be the
gery is the reduced volume of food consumed in one eating
decisive factor.
episode. Human studies are still limited in providing evi-
dence on meal size, but all the available studies are in sup- Patients after RYGB were followed for 2 yr to assess meal
port of positive change. Our research group has recently patterns using verbal report. Number of meals per day was
demonstrated that VSG changes eating behavior and, spe- reported to significantly increase from 4.9 meals/day pre-
cifically, reduces ad libitum meal size, meal duration, and surgery to 5.8 meal/day 1 yr after the operation and to
rate of eating (unpublished work). Similarly, Laurenies et decreased back to the baseline number at 2 yr after the
al. (163) showed that following RYGB meal size becomes operation (5.4 meals/day). The significant change only oc-
significantly smaller. Six weeks after surgery, RYGB pa- curred during the morning meals. Postoperatively, there
tients consume only 42% of the preoperative meal size. was a trend for patients to consume fewer meals at night
After 1 and 2 yr, the meal size increases to 57 and 66% of (163). Increased frequency of meal consumption was in line
the preoperative meal size, respectively (163). Using an ad with the animal data (36, 339).
libitum buffet meal targeting direct behavior, Mette et al.
(212) suggested that the reduction in total calorie intake Increasing the frequency of meals can be a natural compen-
measured 6 mo post RYGB and SG surgery was explained satory reaction, but it can also be a conditioned learned
solely by the reduction in portion size and not by energy behavior to control the unpleasant postprandial physiolog-
density or food choices. Animal studies are important to ical signals that occur after bariatric surgery. Five years
support the evidence due to the confounding effect of after RYGB, patients described going through a “learning”
social factors of wanting to lose weight after surgery in phase during the first year to learn new eating habits includ-
human studies. After RYGB, rats reduce their intake of ing eating smaller and more frequent meals (173). The in-
both liquid and solid diets in the acute and chronic phases crease in frequency of meals do however not compensate for
(339). Two other studies showed positive changes but the calorie deficit patients maintain as would have been
were not conclusive. One study reported strong trends expected if the procedures relied on restriction of the meal
for decreased meal size (⫺30%), but the results did not size only.
reach statistical significance (112). In the only other
study, chow meal size was significantly reduced 5–10 D. Calorie Intake and Energy Density
days but not 11–19 days after RYGB (330). More re-
cently, Mathes et al. (187) supported those findings by Patients after bariatric surgery do not only consume smaller
showing not only a reduction in total daily calorie but portion sizes as previously discussed but consume less total
also from calories consumption from all individual ma- calories per day. In the first few weeks after the operation,
cronutrients from a cafeteria diet, suggesting reduced the postoperative diet generally provides 500 – 800 kcal/
portion sizes. It is important to bear in mind methodolog- day, resembling a very-low-calorie diet. The calorie intake
ical variations where results are apparently contradic- increases gradually between 3 mo to 1 yr from an average of
tory. 800 to 1,000 kcal (152, 200). Total calorie intake increase

AL-NAJIM ET AL.
gradually up to 5 yr postoperation but remains lower than patients after RYGB reported a significant decrease in des-
the preoperative values, albeit not significantly different serts, cookies, and candies consumption, but an increase in
(199). fruits and vegetables. Avoidance of foods containing fat
was also documented for the RYGB group (217). le Roux et
Dietary energy density (DED) is the amount of kilocalories al. (166), using the same methodology and set of patients,
per gram of food (kcal/g) (93). Fat is the biggest influence on showed a decrease in reported preference for fat 6 yr after
DED due to its high energy content, which is more than RYGB in comparison to patients having VBG. Ernst et al.
protein and carbohydrates (9, 4, and 4 kcal/g, respectively). (96) also studied a group of patients who reported a reduc-
On the other hand, water containing foods such as fruits tion in consumption of desserts such as chocolates, cakes,
and vegetables have low DED (118). The consumption of and cookies and an increase in intake of vegetables, poultry,
larger volumes of food without increasing total calorie in- and protein-rich foods such as fish and eggs. Primeaux et al.
take has been shown to affect feelings of fullness (163) and
(235) again used verbal report by deploying a Food Prefer-
may lead to better weight loss outcomes (93, 169, 245).
ence Questionnaire and VAS comparing VSG to RYGB and
After bariatric surgery, DED also decreases significantly
found that VSG decreased the hedonic rating of most ma-
from 1.07 to 0.78 kcal/g at 6 wk and 0.90 kcal/g and
cronutrient profiles as opposed to RYGB, after which
0.96 kcal/g after 1 and 2 yr, respectively. DED does not
changes were more selective. Caution is needed in assessing
correlate with percentage weight loss at any time point
(164). However, viewing the change in calories 5 yr post- these results because follow-up was restricted to 1–3 mo
operation within the context of patients having lost and and the sample size was small. Postoperative diet changes
maintaining 20 –30% body weight loss patients are con- dramatically within 3 mo, and this could affect the interpre-
suming much less than expected, were they to be experienc- tation of the results (280).
ing a physiological drive to reestablish body fat at the pre
operative set point. In contrast, a number of other studies have reported no
changes in food preference after RYGB and VSG. A retro-
spective cross-sectional study compared food intake and
E. Food Preferences food preferences over 1 yr, and patients reported no differ-
ence in dietary intake and food preferences between RYGB
Changes in DED after surgery necessarily imply changes in and VSG groups (90). This agrees with the longest fol-
the type of food eaten. Halmi et al. (130) were the first to low-up study of 5 yr also comparing VSG and RYGB (199)
suggest that gastric bypass causes a change in macronutri- where patients reported the percentages of macronutrients
ents selection as patients reported they consumed fewer were not significantly different between the two surgical
calorically dense and carbohydrate-rich foods. These re- groups (199).
sults led other researchers to investigate the effect of bari-
atric surgery on food preferences and macronutrient con- Other studies also report that bariatric surgery does not
sumption. Halmi’s results on RYGB were supported over lower consumption and preference for sweet and fatty
the years by other short-term studies (34, 67, 152, 161, 201, foods. A study by Troslter et al. (306) found the opposite
293) and even studies up to 8 yr after RYGB (161). Most of with an increase in fat and decrease in protein intake after
these relied on verbal report. Another recent 2-yr follow-up surgery, while Bavaresco et al. (19) studied patients who
study carried out by Coluzzi et al. (62) assessed changes in reported an overall decrease in intake of all three macronu-
food intake associated with changes in taste again using
trients (carbohydrates, lipids, and protein), with no specific
verbal reports. Six months after surgery, daily caloric intake
preference to any macronutrient after surgery.
reduced by 68% and the reduction was maintained for 24
mo. In addition, 75% of the patients reported a change in
The major limitation is that most human studies rely on
taste associated with reduced interest in sweets, high-fat
indirect verbal reporting which have high risk of underre-
food, and alcoholic drinks (62). As VSG is becoming more
popular, studies on its effect on food preferences are now porting particularly as bariatric patients are asked by mul-
also becoming available. Ammon et al. (7) used verbal re- tiple healthcare professionals to eat less fat and sugars. An-
port by implementing a Food Preference Questionnaire and imal studies allow us to examine changes in food prefer-
VAS to assess changes in preference for different types of ences without being the confounding factor of social
food varying in their macronutrient composition 6 wk after pressure. Interestingly, animals behave similarly to many
VSG and found postoperative hedonic ratings decreased for of the reports from humans after RYGB. Bueter et al. (38)
foods high in fat and carbohydrate content. and le Roux et al. (166) used two-bottle preference test
and found a significant reduction in the consumption of
When comparing RYGB with BAND or vertical banded fat and sugar solution compared with sham-operated
gastroplasty (VBG), Olbers et al. (217) used verbal report rats. Rats after RYGB also showed an increased prefer-
by implementing the SOS (Swedish Obese Study) question- ence for a vegetable drink over low-sucrose and low-fat
naire to compare RYGB and VBG at 1 yr postsurgery. The liquids as demonstrated by Seyfried et al. (265).

Furthermore, when rats after RYGB were presented with a

solid diet, an initial increase in preference for the high-fat
chow was observed, which then decreases to 51% of that
seen in sham-operated rats (249). This suggests the exis-
tence of an underlying mechanism for the “conditioned” Food frequency
shift in the chow preference. Mathes et al. (187) assessed the Postprandial discomfort
Fullness
preference for diets consisting of different macronutrients
composition, using a cafeteria study. The results indicated a
progressive reduction in the proportion of calories from fat,
but despite this dietary shift to lower fat consumption after
RYGB, both the RYGB as well as sham-operated rats con-
tinued to select the majority of their calories from the high- Food Intake after bariatric surgery
fat/high-sugar options (187). This is an important outcome
leading to the hypothesis that changes in food preferences
after RYGB may not result of the hedonic value of food
after RYGB, but rather influenced by learning that too
much fat may have negative visceral consequences. Food volume
Energy density
The only human study that tried to mimic the rigorous Calorie intake
experimental protocol in rats found that 6 mo after RYGB Hunger
and VSG humans consumed 50% fewer calories when of-
fered a buffet lunch, but that the macronutrient composi-
tion of these meals was similar to before surgery. An impor-
tant difference between the rodent and human cafeteria diet
FIGURE 4. Changes in food intake after bariatric surgery.
or buffet meal studies was that the rodents were tested when
they were weight stable, while the humans were still in a
negative energy balance and thus the humans were eating so
few calories that they may not have triggered the threshold We progress through satiation as our gut signals accumu-
where negative visceral consequences would necessitate late and indicate increasing loading with energy and nutri-
them to reduce the proportion of fat in their diet. ents. However, hedonic responses accompanying certain
foods can override the signal to terminate intake that arises
FIGURE 4 presents the direction of change of food intake even with complete satiation.
after bariatric surgery.
A. Mechanisms That Explain Reduction in

VI. MECHANISMS OF CHANGED EATING Calorie Intake
BEHAVIOR
1. Hypothalamic and nucleus tractus solitarius
Food intake is an innate behavior regulated by two comple- signaling
mentary drives, the homeostatic and hedonic pathways
(251). The homeostatic pathway controls energy balance by In the hypothalamus, the arcuate nucleus (ARC) is the main
increasing the motivation to eat following depletion of en- region involved in the homeostatic control of food intake
ergy stores or alternatively meal termination in response to (258). Within the ARC, two groups of neurons are promi-
physiological satiation signals (27). In contrast, hedonic or nently implicated in the regulation of feeding. One group
reward-based regulation is related to the sight, smell, and localized more laterally in the ARC coexpress anorexigenic
taste of food, along with emotional and social factors, all of (appetite suppressant) neuropeptides, i.e., cocaine- and am-
which integrate to impact on food intake (27). The hedonic phetamine-related transcript (CART) and proopiomelano-
pathway can override the homeostatic pathway during pe- cortin (POMC) (311). The second group of neurons cluster
riods of relative energy abundance by increasing the desire more medially in the ARC, coexpressing orexigenic (appe-
to consume foods that are highly palatable (27). tite stimulant) neuropeptides, i.e., neuropeptide Y (NPY)
and agouti-related protein (AgRP) (311). Neuronal projec-
Satiation is the process that culminates in termination of an tions from the ARC then communicate with other key hy-
eating episode and is achieved by prandial and postprandial pothalamic regions, such as the paraventricular nucleus,
signals that are generated when nutrients are absorbed from dorsomedial nucleus, and ventromedial and lateral hypo-
the small bowel into the peripheral circulation (30). Satia- thalamic nuclei (205, 311). The ARC has an incomplete
tion is an unconditioned behavior; it cannot be controlled blood-brain barrier that allows direct nutritional informa-
by the taste of food or whether the food is rewarding or not. tion from the periphery to be sensed as well as indirect

AL-NAJIM ET AL.
peripheral markers of ingestive physiology such as insulin, release is not observed after BAND which appears to rely on
leptin, and gut hormones to gain access to the signaling pressure on the IGLES and vagal signaling to reduce hunger
pathways that regulate appetite in the ARC (193). In addi- (165).
tion, the vagal nerve transmit peripheral signals produced in
the gastrointestinal tract to the nucleus of the tractus soli- Similarly to PYY, GLP-1 is also secreted by the L cells of the
tarius (NTS) in the brain stem where signals then integrate small bowel in response to a meal to decrease food intake
with those of the hypothalamus to control appetite (253). through its effects on the hypothalamus and brain stem
(295). Its physiological function on food intake and blood
Enhanced hypothalamic and NTS signaling has been pro- glucose has been postulated to be through its effect on gas-
posed as an underlying mechanism for the reduced appetite tric emptying, glucagon release, and secretion of insulin
and thus weight loss after bariatric surgery. Interestingly, from the pancreas (incretin effect) (248). Despite the phys-
despite the reduced food intake and body weight of differ- iological benefits of GLP-1, on its own it is not good enough
ent bariatric procedures, the majority of studies found an to explain all the effects of bariatric surgery (331), suggest-
upregulation of NPY and AgRP and unchanged POMC ing the appetite change after bariatric surgery is a result of a
levels (16, 208, 318). Stefater et al. (287) found unchanged synergistic response of multiple gut hormones (233).
NPY and AgRP expression after VSG in rats. However,
AgRP increased in pair-fed rats (287), suggesting that the 3. Bile acids
calorically restricted rats were hungry and the VSG rats
were not (198). Another study by Romanova et al. (246)
observed lowered levels of NPY 10 days after RYGB and in As far back as 1968, controlled studies of administration of
pair-fed controls compared with sham surgery. These ap- bile acids indicated that elevated circulating bile acids could
parently contradictory findings may relate to differences in suppress food intake (32). The physiological handling of
study periods examined (i.e., an acute vs. a chronic setting) bile acids in the small bowel has in more recent times been
or differences in transcriptional processing between the end linked to appetite and metabolic control through recogni-
point used as surrogates of orexigenesis (16). Barkholt et al. tion that bile is a potent endogenous stimulant of the endo-
(16) investigated the effect of RYGB on second-order crine L cell, liberating the satiety gut hormones PYY and
downstream orexigenic melanin-concentrating hormone GLP-1 (230). In humans, postprandial bile acids are posi-
(MCH) mRNA expression finding that RYGB but not pair- tively correlated with the circulating levels of some anorex-
fed rats had blunted MCH expression in the lateral hypo- igenic gut hormones (GLP-1 and PYY), but negatively cor-
thalams. This suggests that RYGB surgery puts a “brake” related with the orexigenic gut hormone (ghrelin) (242).
on orexigenic hypothalamic output signals as the hunger Bile acids can engage and activate the nuclear farnesoid X
signals arising from the ARC do not translate into sensa- receptor (FXR) and cytoplasmic G protein-coupled BA re-
tions of hunger nor into food-seeking behavior, potentially ceptor TGR5 (314). The activation of TGR5 in the gut
due to a reduced mesolimbic dopaminergic neurotransmis- stimulates the release of GLP-1 and PYY (15). On the other
sion (16). hand, activation of FXR by bile acids promotes the release
of fibroblast growth factors FGF19 and FGF21 (57). FGF21
2. Gut hormones mediates simple sugar consumption by reducing the appet-
itive behavior towards sweet food (315).
Bariatric surgery involves a profound anatomical change to
the gastrointestinal tract (247, 263), which causes a more Following gastric bypass, the levels of total plasma bile acid
rapid delivery of nutrients to the distal small bowel (49, are elevated (225); this is postulated to be due to the ana-
192, 313). As a result, gut adaptation facilitates an exag- tomical changes causing a prompt supply of undiluted bile
gerated rise in a number of peripheral satiety hormones to reach the distal L cells and activating the TGR5 recep-
including PYY and GLP-1, and reduced rise of the hunger tors. Bile acid metabolism is also markedly changed after
hormone ghrelin occurs within days after bariatric surgery RYGB, due to changes in bacteria-driven transformation
(70). Those hormones have receptors in the peripheral sys- and deconjugation and changes in hepatic extraction of
tem and in the CNS forming a gut-brain hormonal axis. recirculating bile acids (111). Primary bile acids are synthe-
sized and conjugated in the liver (87) and then deconjugated
PYY is released from the L cells of the distal small bowel and dehydroxylated to secondary bile acids by the gut mi-
after a meal in proportion to the consumed calories (18). crobiota when exported to the small intestine (52). Signifi-
After bariatric surgery, the postprandial levels of PYY are cant increases in the 12␣-hydroxylated/non-12␣-hydroxy-
elevated and the new levels correlate with the postoperative lated bile acid ratio have been described after RYGB. Cir-
weight loss (79, 191). The importance of PYY in the regu- culating bile acid profiles are not altered after BAND (156,
lation of feeding after RYGB has also been investigated 223, 230, 273) as there is no change in the pathway of
using octreotide, which blocks the release of most of the gut nutrients reaching the small bowel. In the normal anatomy,
hormones in humans and rats and, not surprisingly, in- bile acids are diluted and mixed with chyme and therefore
creases food intake (103, 115, 168). Exaggerated hormonal are less likely to stimulate L cells for peptide secretion. VSG

does however also cause elevations in the levels of bile acids Liou et al. (174) have examined whether changes in the gut
possibly due to the increased gastric emptying (288). microbiota after RYGB are conserved across rodents and
humans and whether transplantation of RYGB modified
4. Gut microbiota microbiota can confer a transferable weight loss effect on
recipients. With the use of the diet-induced obesity-suscep-
tible C57BL/6J strain of mice a decrease in body weight of
Gut microbiota contributes to many physiological func- 30% was observed by 3 wk after RYGB. Food intake did
tions such as the production of short-chain fatty acids not differ between GB and SHAM groups, but increased
(SCFAs) (177), neurotransmitters (68), and regulation of fecal calorie loss occurred in the GB group signaling energy
gastrointestinal hormones (80, 143), which has led some wasting. Principal component analysis revealed that distal
researchers to consider it as a virtual organ on its own (58, gastric, ileal, cecal, and colonic microbiota were strongly
99, 107). modified by RYGB. Unique changes after RYGB not seen
after matched nonsurgical weight loss included increases in
The interest in the role of gut microbiota in the development Enterobacteriales and higher Verrucomicrobiales. Three
of obesity started with findings of intestinal bacterial colo- phylum level increases predominated in Bacteroidetes, Ver-
nizations that aid energy conversion into body fat (308). rucomicrobia, and Proteobacteria, with resolution to the
Bäckhed et al. (13) showed that germ-free (GF) mice can genus level of Alistipes, Akkermansia, and Escherichia. Re-
consume a higher number of calories but remain leaner than cipient lean, germ-free mice inoculated with cecal contents
conventionally raised mice. Moreover, transferring the mi- from RYGB-operated animals had reductions in adiposity
crobiota from conventionally raised mice to GF mice causes not seen after transplantation of microbiota from animals
a sharp increase in body fat even with low food intake (13). that had undergone food restriction-driven weight loss.
Phylogenetic analysis of gut bacteria of three human groups Shotgun sequencing of the human fecal metagenome to
(healthy weight, obese, and post-RYGB) showed six main functionally analyze the gut microbiota of weight-stable
bacterial phyla to be present. The majority of the bacterial women 9 yr after RYGB was conducted by Tremaroli et al.
sequencing were among Firmicutes and Bacteroidetes, with (305) and was coupled to human-mouse microbiota trans-
the rest distributed among Proteobacteria, Actinobacteria, plantation experiments. An increased presence of Gamma-
Fusobacteria, and Verrucomicrobia. Those bacterial phyla proteobacteria was notable after RYGB, while lower levels
are distributed differently in the intestines of the study within the Firmicutes phylum of Clostridium difficile, Clos-
groups. Prevotellaceae and Erysipelotrichaceae subphylum tridium hiranonis, and Gemella sanguinis were recorded
of Bacteroidetes and Firmicutes, respectively, are mostly after RYGB. Conversely, facultative anaerobes within Pro-
abundant in obese individuals; in fact, Prevotellaceae is teobacteria (Escherichia, Klebsiella, and Pseudomonas)
only found in obese individuals and is considered “obese were increased in relative abundance in RYGB recipients.
specific.” In contrast, Fusobacteria and the family Entero- Metabolomic comparisons revealed a decrease in SCFA/
bacteriaceae within Proteobacteria were found only in the branched-chain fatty acid ratio after gastric bypass, indicat-
RYGB group. This suggests that after bariatric surgery, paring increased amino acid fermentation. Genetic signatures
ticularly RYGB, the profile of the microbiota is substan- for microbial enzymes involved in the generation of second-
ary bile acids were increased and correlated with shifts in
tially altered (336). A recent meta-analysis study by Magou-
the ratio of secondary to primary bile acid profiles occurring
liotis et al. (180) reviewed 22 studies and 562 patients who
in recipients of RYGB microbiota, suggesting altered bile
underwent different bariatric procedures. Despite finding
acid profiles may participate in reductions in adiposity after
considerable variation in the documented bacterial species
surgery.
in different studies, the overall findings also support a post-
operative shift of the gut microbiota (180). This alteration
in abundance and diversity of gut microbiota is speculated B. Mechanisms That May Explain Reduction
to cause the shift in bile acid composition discussed above. in Calorie Density of Food
The mechanisms behind altered gut bacteria are not com- Humans and animals have innate preferences for nutritive,
pletely understood, but a role of the new dietary macronu- calorie-dense food that provide them with the essential en-
trient composition, anatomical manipulations that change ergy (259). Their biological system, however, is geared to-
the levels of oxygen in the intestines, and pH and bile flow, wards learning when consumption causes postingestive
have been suggested. On the contrary, alteration in gut malaise, and subsequently these foods may be remembered
microbiota may not be a result of weight loss after bariatric as harmful or “not good” for subsequent meals (259). After
surgery, but rather a cause of weight loss. An emerging bariatric surgery, food containing fat and simple carbohy-
concept suggests that metabolic regulation starts from the drate may be labeled as “not good” due to negative
gut and then sends signals to the brain, and other endocrine postingestive sequelae. This can result in altered food pref-
organs (104). erences observed after bariatric surgery as described in sec-

AL-NAJIM ET AL.
tion IVD. The mechanism behind this alteration is postu- increased total food intake with no specific changes in food
lated to be due to visceral signals and changes in taste func- selection or preference (59).
tion.
Orexin neurons (A and B) are activated in anticipation of
1. Neural and hormonal signals palatable food rewards (133), illustrating the ability of the
orexin system to respond not only to internal energy bal-
A) NEURAL SIGNALS. Similar to satiety regulation, macronutri- ance cues but also to external environmental cues linked to
ent preferences are also controlled by neural and hormonal the cognitive aspects of feeding and food reward behaviors.
signals as part of the food intake regulation system. This On that basis, Clegg et al. (59) demonstrated that central
section will summarize the available literature on the effect administration of orexin-A in rats prompted rats to choose
of neuropeptide and hormonal peptide on food choices. a high-fat diet instead of a low-fat one, suggesting a role of
orexin-A in controlling food selection.
Evidence from pharmacological and genetic data suggests a
role of POMC in eating behavior, particularly dietary fat The endocannabinoid system also plays a role in food
consumption. Tung et al. (307) found that POMC genotype choices (220). The cannabinoids [anandamide (AEA) and
was a strong predictor of dietary fat preference with POMC 2-arachidonoylgycerol (2-AG)] are important carriers of
null mice choosing to eat approximately twice as much fat, metabolic information between the CNS and the periphery
but similar amounts of carbohydrate and protein compared (78). Within the reward circuitries, they interact with opi-
with wild-type mice. Human studies validating this infor- oid and dopaminergic systems to enhance satisfaction com-
mation are scarce. However, a genome-wide scan based on ing from the ingestion of palatable food (220). Pérez et al.
data derived from food questionnaires collected from Mex-
(98) used intraperitoneal injection of the CB1 receptor ag-
ican-American families suggested that human chromosome
onist N-(2-chloroethyl)-5Z,8Z,11Z,14Z-eicosatetraen-
2p22, which is a region containing POMC, was linked with
amide (ACEA) in rats and showed increased ingestion of a
increased saturated fat intake in those families (45).
carbohydrate diet but not fat or protein. Rimonabant, a
selective CB1 receptor antagonist, was a medication devel-
As with most neuropeptides, studies on food choices are
oped for the treatment of obesity but withdrawn later from
limited and, therefore, the effect of CART on food selection
the market due to its adverse effects, which included anxi-
is not yet determined. Deletion of the CART gene in mice
ety, depression, and suicidal ideation (56, 203). In a func-
did not cause a change in sweet preference compared with
tional magnetic resonance imaging (fMRI) study of healthy
wild-type mice, suggesting that either CART peptides do
not modulate food preference or that compensatory normal-weight volunteers, rimonabant was shown to alter
changes in CART gene modified mice have obscured this the brain activation of key reward areas towards the sight
phenotype (66). and smell of rewarding foods (144). Direct measures of
food preferences in rimonabant-injected rats also showed
Orexogenic neuropeptides may play a more significant role supporting findings of reduced preference (186, 236) and
in food choices. AgRP-regulated appetite is affected by the motivation to palatable food choices (274).
opioid pathways, in which the hedonic and reward aspects
of feeding are implicated. Naloxone, a nonselective opioid TABLE 1 summarizes the effect of appetite neurotransmit-
antagonist, blocks AgRP-induced feeding (128, 159). Acti- ters on changes in food preferences.
vation of the opioid system, in turn, has been associated
with increased intake of preferred, high-fat-containing diets B) HORMONAL SIGNALS. Long- and short-term peripheral satiety
(337). Consistent with this, Hagan et al. (128) found that hormones also impact food preferences. However, the im-
AgRP selectively increases the intake of a high-fat diet when pact of hormones like leptin (a long-term peripheral hor-
rats have simultaneous access to two diets differing in their mone) was not as clear as the macronutrients preferences
relative amounts of fat. were different dependent on the age of rats, type of infusion
(acute or chronic), and their baseline macronutrients pref-
Similarly to AgRP, NPY-induced hyperphagia is dependent erences (323).
on opioid receptor activation, which also causes a shift in
food choices (128, 159). Increased consumption of carbo- The effect of insulin on sugar consumption has long been of
hydrates diet is linked to increased levels of NPY in the interest. In 1958, Jacobs et al. (147) found that insulin
hypothalamus. In addition, administration of NPY report- injections in rats resulted in a shift in consumption of sweet
edly increases the consumption of high-carbohydrate diets solutions from 10% concentration to 35% concentrations,
(285, 316). suggesting an increased preference for sweet solutions. In
our current understanding, this is not surprising as insulin-
MCH differs from NPY and AgRP in that its orexigenic induced hypoglycemia promotes the seeking for urgent and
effect does not depend on opioid reception activation. In- quick release source of energy to correct the blood sugar
terestingly, central MCH administration in rats resulted in concentrations.

Table 1. Summary of the effect of appetite neurotransmitters on changes in food preferences

Factor Type of Study Method Food Preferences
POMC Animals (307) Examined Pomc-null, Pomc⫹/⫺, and Increases fat diet; no change in
wild-type mice protein or carbohydrates
Humans (45) Genome-wide scan and Food Frequency Increases saturated fat intake
Questionnaires
CART Animals (66) Two-bottle test in Carttm1Amgen knockout No change in sucrose preference
(Cart KO) and wild-type (WT) mice
AgRP Animals (128) Effect of central administration of AgRP Increases high-fat diet over low-fat
vs. saline into the third cerebral diet; no change in sucrose
ventricle in rats on high-fat, low-fat, preference
and sucrose preference
NPY Animals (316) Rats self-selected macronutrients or High-carbohydrate diets linked with
given a single-diet paradigm followed higher levels of NPY
by measurement of hypothalamic NPY
levels
Animals (285) Effect of NPY injected into the Increases carbohydrate
paraventricular nucleus in rats on consumption; no change in
carbohydrate, protein, and fat diet protein or fat consumption
MCH Animals (59) Effect of MCH injection into the third No change in food selection
cerebral ventricle in rats on high-fat
and low-fat diet
Orexins Animals (59) Effect of orexin-A injection into the third Increases high-fat diet
cerebral ventricle in rats on high-fat
and low-fat diet
Endocannabinoid Animals (98) Effect of intraperitoneal injection of CB1 Increases carbohydrate intake
receptor agonist, ACEA, on protein,
carbohydrate, and fat intake
Animals (186, Effect of CB1 receptor antagonist Reduced preference and
236, 274) (rimonabant) on food choice and motivation to seek palatable food
motivation to palatable food options choices
Humans Effect of CB1 receptor antagonist Reduced brain activation towards
(144) (rimonabant) on brain activation the sight and smell of chocolates
(rewarding food)
Reference numbers are given in parentheses.
Conversely to leptin and insulin, PYY is a short-term pe- (309). In their study, Peters et al. (227) found that exendin
ripheral hormone. Central administration of PYY1–36 in 9 –39 significantly enhanced food intake suppression occur-
satiated rats resulted in an increase in carbohydrate and fat ring after glucose, but not after corn oil or albumin preloads
intake as opposed to protein when given all three macronu- supporting the nutrient selection action. In the diet selection
trients (285). No current studies are available on the effect studies, exendin 9 –39 selectively decreased intake of a high-
of PYY3–36 on food choice. carbohydrate diet, suggesting that blocking GLP-1 activity
leads to a selective feeding response to the carbohydrate
The effect of GLP-1 on the quantity of food intake is well portion of the diet. On the other hand, exendin 4 selectively
evidenced in humans (105, 125) and experimental animals decreased the intake of a high-protein diet (227). Rats
(309). However, its effect on the composition of food intake treated with liraglutide (Victoza/Saxenda), a synthetic
has not been as clear. GLP-1 is a nutrient-specific hormone. GLP-1 receptor agonist used as a type 2 diabetes mellitus/
Its secretion has been reported to be particularly sensitive to obesity treatment, decrease their intake of foods high in
the ingestion of carbohydrates (241) and long-chain unsat- sugar and/or fat relative to laboratory chow (131, 237).
urated fatty acids (244), but slightly if at all sensitive to Only recently, the impact of GLP-1 on macronutrient selec-
proteins (92) and amino acids (64). To investigate if this can tion in humans became available. Blundell et al. (31) found
impact on macronutrient selection, Peters et al. (227) in- that semaglutide caused reduced liking and wanting based
jected rats with exendin 4 and exendin 9 –39. Exendin 4 is a on verbal reports, and reduced intake of high-fat and savory
GLP-1 receptor agonist and exendin 9 –39 GLP-1 is a recep- food in an ad libitum evening snack meal. Hyde et al. (146)
tor antagonist, which both have been used in animal studies however tested liraglutide in a highly controlled cafeteria
in place of GLP-1, due to its short half-life (227). Central diet paradigm to directly measure food choices. They found
administration of exendin 4 in rats has been shown to de- although the GLP-1 analog potently reduced food intake
crease food intake (81, 209, 244a, 309), whereas treatment both when rats were offered a palatable or less palatable
with exendin 9 –39, increases food intake in sated rats diet, it did not alter food preferences (146).

AL-NAJIM ET AL.
Table 2. Summary of the effect of appetite hormones on changes in food preferences

Factor Type of Study Method Food Selection
Leptin Animals (323) Intraperitoneal injection Leptin has different effects on macronutrient preferences,
dependent on age and the type (acute or chronic) of
injection
Insulin Animals (147) Insulin injections Increased glucose preference
CCK No studies — —
PYY Animals (285) PYY injected into the paraventricular nucleus Increases CHO intake, and small (significant) increase in
in rats fat consumption; no change in PRO consumption
PP No studies — —
GLP-1 Animals (227) Intraperitoneal injection of GLP-1 antagonist Exendin 9–39 selectively decreased intake of CHO; exendin
(exendin 9–39) and its agonist (exendin 4) 4 decreased intake of PRO
Animals (146) Once daily injections No alteration in food preferences
Humans (31) Once weekly subcutaneous injection Reduced intake of high-fat and nonsweet snacks
Ghrelin Animals (267) Central injection Increases fat intake over CHO intake
Animals (88) Peripheral administration Stimulates the intake of fat-rich palatable foods
Reference numbers are given in parentheses.
Ghrelin was also linked to changes in food choices. Shim- Once the taste is identified, signals are sent to the NTS in
bara et al. (267) demonstrated increased fat intake and the hindbrain to determine the appropriate responses.
reduced carbohydrate intake after central administration of Responses are classified into aversive or appetitive, de-
ghrelin. Peripheral ghrelin administration also stimulates pending on the effect the stimulus has on the hedonic
the intake of fat-rich palatable foods, whereas blocking the system. Physiological responses are in turn the body’s
release of ghrelin through genetic or pharmacological inhi- way of preparing the digestion and ingestion of that par-
bition results in a decrease in their intake (88). TABLE 2 ticular stimulus (282). Those three functional domains
summarizes the effect of peripheral hormones on changes in (FIGURE 4) are equally important for the function of taste.
food preferences. Therefore, the taste systems can be broken down into
three main functional domains: stimulus identification,
2. Taste function ingestive motivation, and digestive preparation (FIGURE
5) (282).
Taste directly influences eating behavior through its effect
on food preference and food intake. Taste is the sensation A) STIMULUS IDENTIFICATION. The stimulus identification dom-
produced when a substance enters the mouth and reacts ain or “sensory domain” encompasses the sensory function
with the taste receptors cells located on the taste buds. of the taste system to detect “sweet,” “salty,” “bitter,”
Reward
*Consummatory
Reward
*Appetitive
Sensory Reward Physiology
Detection or post-ingestive
Discrimination effects FIGURE 5. The taste domains as described by A. C. Spec-
tor (282).
Taste

“sour,” and “umami” (e.g., monosodium glutamate taste) blood sugar that cause a “satiation effect” towards sweet
tastes. taste and/or neuropathy causing a reduced taste sensitivity
overall (255). A number of studies subsequently established
Taste is detected when the concentration of the tastant that patients with T2DM have higher thresholds for glucose
reaches a threshold level that activates taste receptors to and sucrose detection than patients with type 1 and controls
generate action potentials in gustatory nerve fibers that are (43, 116, 291, 291). In addition, hyperglycemia is associ-
potent enough to elicit a taste perception (124). Taste sen- ated with higher sweet taste thresholds when patients with
sitivity ranges from the lowest concentration of taste stimuli diabetes and pre-diabetes are compared (43, 319).
that can be detected (taste detection thresholds) to the in-
tensity perceived for that stimulus (above-threshold re- Depression and anxiety, common comorbidities of obesity
sponses) (33). (219, 262), also alter taste. Severely depressed patients have
reduced sensitivity to all tastes, most commonly sweet
Taste may contribute to the development of obesity; how- (290), which normalizes on recovery. They also report
ever, it is difficult to assess whether hypogeusia (reduced lower intensity responses to suprathreshold stimuli (8).
taste sensation) causes hyperphagia and weight gain or vice Based on the “monoamine theory of depression,” it is the
versa. Bartoshuk et al. (17) stated, “The obese live in differ- result of a deficiency in circulating monoamine concentra-
ent orosensory and orohedonic worlds than do the tions and hence reduced neurotransmission of norepineph-
non-obese.” rine, dopamine, and serotonin (5-HT), and/or reduced sen-
sitivity of their receptors (140). Taste cells express 5-HT, its
Many studies have shown associations between taste synthetic enzymes, and its receptors. Therefore, 5-HT is
thresholds and weight (202, 269, 272). Kawai et al. (151) involved in the taste signaling by altering ion channel func-
found that leptin, an adipokine, inhibited specific sweet tion. Measurement of taste function in healthy humans
taste responses in lean mice but not in obese diabetic (db/ showed that enhancing 5-HT increased sweet taste sensitiv-
db) mice, suggesting a role of this hormone in sweet taste ity by significantly reducing the sucrose taste threshold by
sensitivity. Kawai et al. (151) found that Ob-R, the leptin 27% (136).
receptor, is also found in the taste cells of circumvallate
papillae in mice in addition to where it has previously been 5-HT is implicated in the development of anxiety and stress
suggested to be present, i.e., the CNS (65), peripheral cells (117). Anxiety and stress, similarly to depression, often lead
such as T cells (175), vascular endothelial cells (317), mus- to increased intake of high sugary food (47, 335) which
cle cells (155), and pancreatic cells (142), indicating that could be a result of the reduced sweet taste sensitivity
taste cells are a site of leptin action (151). Peripheral leptin caused by the reduction in 5-HT (136).
resistance is well described in obese mice and humans as a
mechanism increasing food intake, and whether this phe- Taste stimulation was attributed to be one of the contribu-
nomenon extends into the sensory taste domain is unclear tors to the change in appetite and eating behavior, particu-
(109). Obese rodents and humans have increased levels of larly to the changes in food preferences. De Wys and Wal-
circulating leptin compared with normal weight subjects ters (77) reported a connection between taste changes and
(179). During weight gain, basal plasma leptin levels should food aversions. They found that increased taste acuity for
gradually rise, concomitantly sweet taste sensitivity reduce. urea (bitter) in cancer patients correlated with meat aver-
However, chronic adaptation to high concentrations of lep- sions. Aversions to sweet foods have been associated with
tin may elicit leptin resistance in the taste cells as suggested increases in taste acuity for sucrose (sweet) (39). Based on
by Yoshida et al. (333). This means that any further in- these results, Scruggs et al. (264) were the first to suggest
creases in leptin concentration would not elicit further sup- that the changes in food preferences after RYGB may be
pression (151). attributed to the permutation in taste acuity. To test their
hypothesis, taste detection and recognition thresholds for
Weight loss reduces leptin levels and increases sweet taste the four basic tastes (salt, sweet, sour, and bitter) were
sensitivity, i.e., decreased thresholds, both after invasive, assessed using a modification of the Henkin forced choice
i.e., surgical-induced weight loss (37, 40, 264), and nonin- three-stimulus technique before and after RYGB in women
vasive, i.e., diet-induced weight loss (310), procedures. (137). This technique involves placing drops of water or
Taste sensitivity correlates with reductions in leptin levels tastant on the tongue of the volunteer. The lowest concen-
(310). tration at which the volunteer is able to detect the difference
between the tastant and water represents the detection
Obesity is associated with many related comorbidities in- threshold (137). In this study, Scruggs et al. (264) found
cluding type 2 diabetes mellitus (T2DM). Fabbi (100) was that following gastric bypass surgery, a significant improve-
the first researcher who suggested that patients with diabe- ment in taste acuity for bitter and sour was observed along
tes may have impaired taste function. Later they suggested with a trend toward a reduction in salt and sweet detection
that this abnormality might be due to the elevated levels of thresholds. Methodological limitations of the study include

AL-NAJIM ET AL.
the use of a small sample number (n ⫽ 6), use of tiny tastant “reward domain” comes into play to promote or discour-
drops that causes limited receptor stimulation, and the lack age the ingestion of food (FIGURE 5) (282). The ingestive
of control for the effects of repeated testing. Additionally, motivation domain differs from the stimulus identification
the concentrations of the solutions used were very high, domain in that it represents the hedonic aspects of gustation
especially for sucrose (197). (282). For example, we can distinguish between the differ-
ent taste qualities of food and drinks regardless of whether
Burge et al. (40) used a staircase method of stimulus presen- they are pleasant or aversive by the stimulus identification
tation and found that sucrose recognition thresholds also domain; however, we will only ingest more when it is de-
decreased after RYGB. The group also noted that patients termined to “tastes pleasant” by the ingestive motivation
reported that food tasted sweeter, and they modified food domain.
selection accordingly. Burge et al. (40) also found that pa-
tients who reported an aversion to meat were associated Spector (282) described the taste-related ingestive motiva-
with increased nausea and vomiting. tion as having two subdomains or components: appetitive
behavior and consummatory behavior. Appetitive behavior
Using direct measures of behavior, we investigated the ef- describes the efforts that the subject will undertake to be put
fects of RYGB on the sweet taste sensory domain using a in contact with the food, e.g., searching, foraging, ap-
method of constant stimuli (37) and showed that sweet taste proaching a drinking spout, whereas consummatory behav-
acuity improves after RYGB (37). ior represents the behaviors elicited by the final act when
contact is made with the stimulus (282). Some authors have
Despite all the previous studies showing improvement in equated appetitive behavior to “wanting” and consumma-
taste acuity after RYGB, the change in taste detection tory behavior to “liking” of the stimulus, but it may be
thresholds for sucrose remains controversial. The latest more helpful to consider the actual behaviors as these can
study by Pepino et al. (224) found no change in detection be directly measured experimentally rather than relying on
thresholds for any of the taste qualities [sucrose, glucose, verbal report.
NaCl, and monosodium glutamate (prototypical savory
stimuli)] after RYGB and BAND. The discrepancy between In research, the two ingestive behavior components can be
the earlier studies may be due to differences in the method- studied in combination but also in isolation, depending on
ologies employed to measure taste thresholds, variation in the outcome required. The brief access test is an experi-
the diet composition of subjects at the time of testing, time mental test used for measuring both components of the
from surgery, and sex differences. ingestive motivation domain (324). In this test, a very
small sample of the tastant is presented for a brief dura-
The current literature lacks any studies on taste detection in tion (e.g., 10 s) and the animal’s licking responses are
VSG. Our research group carried out the first taste detection measured using a lick monitoring system (gustometer)
experiment on VSG adolescents in Saudi Arabia by follow- (324). Therefore, it allows measurement of the amount of
ing the same protocol we have previously used on RYGB effort the animal is prepared to undertake to approach
patients (37). We found that VSG did not have an effect on the spout (which may broadly equate to “wanting” the
the detection threshold for sucrose in adolescent patients taste stimulus), and also measurement of the repetitivity
(G. Abdeen et al., unpublished work). Our results suggest per unit time of tongue protrusions over the duration of
that VSG might not fundamentally shift the sensory domain the test (equating to “liking” the stimulus) (3). The ben-
of taste, but food preference changes may instead be related efit of the brief access test is that it minimizes any
to other factors such as conditioned avoidance. postingestive effects of the taste stimuli as only small
amounts are ingested (278, 283).
Several gut peptides, including GLP-1 (102), NPY (338),
glucagon (94), and ghrelin (270) are secreted in response to When the appetitive and the consummatory behavior com-
various taste stimuli and may contribute to taste quality ponents of the ingestive motivation domain are studied in
coding (82, 113). A recent study by Takai et al. (298) found isolation, different experimental tests and tools are re-
that GLP-1 is released from the sweet-sensitive taste cells quired. The appetitive behavior can be assessed using the
(T1R3) immediately after stimulation with sweet com- progressive ratio task (PRT) which was originally designed
pounds, suggesting that GLP-1 might stimulate sweet-sen- by Hodos in 1961 for the use in animal studies (141). This
sitive gustatory nerve fibers. RYGB and VSG patients have task was adopted for the use in human studies for the same
increased postprandial GLP-1 levels (165), which may con- purpose (196). During this task, the subject is required to
tribute to the increased sweet taste sensitivity reported pre- perform a certain number of responses to obtain a rein-
viously (37, 40, 264). forcer (i.e., a reward). After consumption of each reward,
the response demand progressively increases until it is so
B) INGESTIVE MOTIVATION. When a taste is detected in the stimulus great that the subject stops responding. This is referred to as
identification domain, the ingestive motivation domain or the breakpoint and represents the reward value of the rein-

forcer. The PRT is thus an assessment of appetitive respon- In 2012, Mathes et al. (185) also used a brief access test with
siveness (196). gustometer. Surprisingly, they showed almost a doubling in
the appetitive behavior of rats after RYGB for sweet stimuli
Consummatory behavior can be assessed using a taste reac- (185, 339). Although not quite the same outcome, Mathes
tivity test (3). This test has been used in animal studies, et al. (184) repeated the experiment using (PR) lick operant
where an intraoral cannula infuses a taste stimulus directly to study the effect of RYGB in rats on the reinforcement
into the oral cavity and the facial reactions are videotaped value of palatable fluid stimuli. After surgery, RYGB oper-
and analyzed by the investigator (122). Common ingestive ated rats did not show lower breakpoints than SHAM rats
(i.e., positive) animal reactions include tongue protrusions for reinforcers consisting of Ensure, sucrose, or 5% Intr-
and paw licking. While the common aversive (i.e., negative) alipid, even though they had blunted preferences for these
reactions include gapes and chin rubbing (21). Our research caloric fluids versus water in two-bottle preference tests
group has adopted this test for the use in human obesity (184). Those results are also supported by the work of Wil-
studies (G. Abdeen et al., unpublished work). In this human son-Pérez et al. (325) on VSG rats for fat or a carbohydrate
study, a 50-ml chocolate milkshake flowed directly into the food reinforcer. Collectively, those studies started to shift
subjects’ mouths using gravity to deliver a rate of 25 ml/ our thinking that bariatric surgery may not cause changes in
min. Subjects’ facial expressions were recorded on a camera food preferences due to altered palatability of foods but
and were later analyzed using a Facial Expression Food rather due to a learned adjustment to altered postingestive
Preference Rating Scale (G. Abdeen et al., unpublished feedback.
work). Common ingestive human facial reactions to pleas-
ant stimuli include tongue protrusion, mouth movements, The discrepancies with human studies are intriguing and
and ingestion of the stimuli. While aversive facial reactions raise the question of whether, despite best efforts, patients
include gaping, head shaking, wrinkling of the nose, retrac- may still behave in a specific way to “please” the investiga-
tor, a problem that is not seen in rats. An alternative expla-
tion of the head away from the source, and fluid expulsion
nation may be that humans were studied in an acute nega-
(89, 121, 289).
tive energy balance phase while rats were studied when they
were maintaining weight loss and were in a stable energy
C) APPETITIVE BEHAVIOR. To objectively assess the role of this
balance phase.
taste subdomain on changes in the food preferences ob-
served after bariatric surgery, Miras et al. (196) used the
D) CONSUMMATORY BEHAVIOR. This ingestive behavior is actioned
PRT in patients before and after RYGB surgery. He
by the reward value of the stimuli tasted. When food is in
found that the surgery resulted in the selective reduction
the oral cavity, the taste signal is sent to the orbitofrontal
of the reward value of a sweet and fat tastant. Our re-
cortex in the CNS to encode the reward value of a food
search group has also found the same results after VSG
stimulus. The orbitofrontal cortex further communicates
surgery in adolescents (G. Abdeen et al., unpublished
with other limbic structures such as the ventral tegmental
work). area, nucleus accumbens, amygdala, hippocampus, and
ventral striatum with dopamine acting as the primary neu-
Importantly, employing the same task in animal models of rotransmitter. This hedonic activation has led many re-
RYGB and VSG expands our understanding of the mecha- searchers to focus on neuroimaging in the form of fMRI and
nisms that underlie the change in behavior (196). In animal positron emission tomography scans to investigate the
studies, there have been mixed findings as some have shown changes in the hedonic value of food after RYGB.
increases in appetitive responsiveness to sweet-tasting or
fatty stimuli but other studies have not. Tichansky et al. Indeed, a number of studies have found that RYGB is asso-
(304) attempted to assess taste sensitivity in rats using a ciated with decreased hedonic value for food after RYGB
brief access test with gustometer consisting of different su- and particularly sweet or highly palatable foods (215, 257).
crose concentrations. While this experiment may not be These were well-structured studies and showed promising
appropriately designed for the assessment of “taste sensitiv- results but did not particularly assess consummatory behav-
ity,” the result can be interpreted to reflect the “appetitive ior, i.e., the liking and disliking of food; they were also
behavior” to different sweet concentrations. In this study, based on visual and auditory cues, not taste, and therefore
the overall mean licks for the five different sucrose concen- are not actual ingestive behavioral in response to a food. In
trations did not differ significantly. Rats showed a signifi- a step forward, Ochner et al. (216) used VAS and fMRI
cant reduction in the mean licks over a 10-s period for the scans to correlate brain activation with the rating of the
highest three concentrations. Nevertheless, they still had a desire to eat “wanting” and “liking,” though it was also
considerably high mean licks compared with water or with based on visual cues and not real food stimuli. The group
the low sucrose concentrations, suggesting that the rats still found that “liking” of food was not changed despite the
worked harder for the sweeter stimuli than they did to com- reduction in hedonic activation. Scholtz et al. (256) com-
pletely avoid them (304). pared RYGB to BAND patients and found that RYGB

AL-NAJIM ET AL.
caused a greater reduction in the activation of brain reward Berthoud et al. (28) provided three concentrations of su-
areas to high-energy food pictures. In addition, this work crose solution to lean, sham-operated obese, and RYGB
associated the hedonic brain activation with the rating of rats. Lean and sham-operated obese rats showed a right
high-sugar/high-fat food ingestion and found that lower shift of the concentration-response curve, and RYGB rats
hedonic brain activation was associated with the rating of had an essentially flat curve, with more responding to the
ice cream ingestion as “less pleasant to eat” in the RYGB lowest, and less responding to the highest, sucrose concen-
group (256). The findings of this study were explicable by tration (though not significantly different) (28).
differences in the anorexigenic plasma gut hormones
(GLP-1 and PYY), plasma bile acids, and symptoms of Taste plays an important role in pre-
E) DIGESTIVE PREPARATION.
dumping syndrome (256). paring the body for the digestion of a meal. Once the food is
present in the mouth, a number of physiological reflexes can
Faulconbridge et al. (101) compared the neural response to take place as part of cephalic phase responses (FIGURE 5).
pictures of high- and low-calorie foods (HCF and LCF), Salivation is the most obvious cephalic response (190) and
before and 6 mo after RYGB and VSG and in nonsurgical can be triggered by the mere thought of food but increases
weight-stable control participants. Liking ratings for HCF mostly when food is present in the oral cavity (240). Powley
decreased significantly in the RYGB and VSG groups but (234) suggested that cephalic phase responses are increased
remained stable in the control group, indicating reduction with the appetite for food; however, subsequent studies
in liking of highly palatable foods after obesity surgery. found that salivation rate is not actually dependent on the
However, blood oxygen level-dependent (BOLD) response level of hunger (55, 210). The rate of salivation does differ
in the ventral tegmental area (VTA) to HCF (vs. LCF) de- based on the taste of stimuli, with the highest saliva stimu-
clined significantly more at 6 mo in RYGB compared with lation produced by a sour taste, followed by salt, sweet, and
control participants but not in VSG participants (101). bitter (72, 154). Salivation rates are increased with higher
There was no significant changes in any of the other regions concentration of the stimuli (110, 320). A number of studies
relevant to reward processing (101). have suggested that body weight can affect salivation, with
people with obesity having a higher salivation rate; this may
Another method used to explore consummatory taste be- be explained by people with obesity having higher re-
havior in RYGB patient is the Sweet Taste Palatability Test. sponses to food cues and higher food reinforcing value (95,
In this test subjects rate different sucrose concentrations 126, 213). People with obesity also have a slower habitua-
using VAS or global Label Magnitude Scales (gLMS). In tion rate (reduced salivation to the same ingested food)
patients after RYGB, no changes in the sucrose concentra- which can partially contribute to increased food intake (95,
tion that is considered as “just about right” were detected 303).
when comparing patients before and after surgery (37). On
the contrary, Pepino et al. (224) carried out a modified Additional evidence supports the existence of other taste-
version of this test on RYGB and BAND patients and found related physiological reflexes such as delayed increase in
that RYGB surgery, but not BAND, affected the consum- blood triacylglycerol levels (189) and secretion of gastric
matory component of sweet taste perception, characterized acid (148) as well as amylase, gastrin, CCK, glucagon, and
by a rapid shift in sweetness palatability from pleasant to pancreatic polypeptide (327). Another taste-related ce-
unpleasant when repetitively tasting sucrose. phalic response is preabsorptive insulin release, which has
been studied extensively in animals (24 –26, 271) and hu-
The taste reactivity test can also be used to assess facial mans (176, 243, 301, 302). Measuring preabsorptive insu-
expressions for liking and disliking of sweet/fatty stimulus. lin release can be challenging and require a large sample size
This test has not been used in RYGB patients as yet, but we and careful protocol consideration as suggested by Teff et
completed a pilot study to investigate facial expressions in al. (302).
obese adolescent VSG patients in response to high-fat/high-
sugar food stimuli (unpublished work). We used the facial Food odors stimulate cephalic phase responses (332). Using
expression method to assess changes in the consummatory the threshold-discrimination-identification (TDI) test, Juro-
behavior relating to a single, specific food item after VSG wich et al. (148a) found a significant increase in olfactory
surgery. VSG resulted in increased negative (dislike) facial function 24 wk after sleeve gastrectomy (SG), but not after
expressions and decreased positive (liking) facial expres- RYGB. Richardson et al. (239) also did not show improve-
sions for a chocolate milkshake stimulus. In addition, facial ment in olfactory function following RYGB, using cross-
expressions remained unchanged across a similar test-retest cultural smell identification test (CC-SIT). More studies on
interval in nonsurgical control subjects. On the other hand, changes in cephalic phase responses after bariatric surgery
animal studies by Shin et al. (268) found more positive are needed to expand our understanding of this domain.
orofacial responses to low concentrations of sucrose but
fewer to high concentrations after RYGB, indicating re- FIGURE 6 presents the integration of the three functional
duced consummatory behavior for higher sweet stimuli. domains of taste in eating behavior.

Psychological traits, cognition,

and learned behavior
Social and
environmental triggers
n FIGURE 6. The integration of the three functional do-
io
ct
mains of taste (stimulus identification, ingestive motiva-

te
de
Pe
Pr
n
tion, and digestive preparation) in eating behavior.

io
e-
rip
e
at
ab
st
Black arrows represent triggers of eating behavior,
he
liv
Ta
so
Sa
ra
un
green arrows represent response signals from the
rp
ls
ge
tiv
ig
Reward value for taste
brain to initiate or terminate an eating episode, and
ra
na
in
nd
ls
orange arrows represent cephalic phase responses.
su
sa
lin
The three functional domains discussed above inte-
tie
re
ty
le
grate together via multiple signals sent to the brain to
si
as
gn
e
determine the reward value for taste of the ingested
al
s
food. The ingestive motivation domain can influence in-
gestive behavior by any or all of the following: 1) the
metabolic (e.g., hunger, thirst), 2) the oro-sensory
(e.g., taste, texture), and 3) the postabsorptive (e.g.,
Ap
glycemic excursions, satiation) dimensions. Any change

pe
tit
to one or all of the stimulus identification, ingestive

iv
e
motivation, and digestive preparation domains can also

be
ha
alter eating behavior and thus obesity.

vi
C
or
on
su
m
m
at
or
y
be
ha
vi
or
C. Other Contributing Mechanisms The acquisition of conditioned taste aversion occurs when
the subject associates the novel taste of a new sickness-
Memory impacts on food intake and preferences. As hu- inducing food (unconditioned stimulus) with nausea gener-
mans and animals evolved, they had to learn which food in ated from its consumption (unconditioned reaction). “Un-
the wild was safe or not safe to eat (322). Taste provides conditioned” is a term used for first time exposure to the
critical initial signals about the safety of the food. Sweet stimulus and reaction. However, future exposures become
taste often indicates that the food is energy dense and safe, “conditioned” as the subject has learned what reaction
whereas bitter taste often indicates toxicity and potentially could be expected (322). Avoiding the conditioned stimulus
hazards (76). However, taste is only the initial indication; altogether in the future is a sign of an established condi-
once the food is consumed further consequences can be tioned aversion reaction (322).
generated. For example, nutritious food will suppress hun-
ger and provide energy, and therefore, it will be labeled as In contrast, conditioned taste avoidance refers to the con-
“familiar and safe.” If the food results in significant gastro- scious avoidance of food that is still palatable but has
intestinal malaise, it will be labeled “familiar and not safe,” caused adverse reactions when larger quantities are con-
which is referred to as conditioned taste aversion (260). sumed, for example, lactose intolerance or nut allergy.
Conditioned behavior is of a particular interest in obesity Studies with rats indicate that the two terms “conditioned
and obesity surgery studies as patients often report changes taste avoidance” and “conditioned taste aversion” should
in their likes and dislikes of certain types of food. In this not be used interchangeably as they are different processes
section, we review the difference between aversion and (221). Aversion to food is accompanied by a strong dislike
avoidance of certain types of food and their possible mech- or disinclination to the stimuli with almost complete resis-
anisms. tance to any ingestion, whereas avoidance of food happens
as the subject starts ingestion but then stops the consump-
1. Conditioned aversion versus conditioned tion of the food subsequently despite its palatability.
avoidance
Facial and somatic reactions of rats were used to determine
Conditioned taste aversion is a form of classical condition- taste avoidance and aversion in a taste reactivity test (TR
ing, which is the simplest form of associative learning (322). test), which is a classic technique to investigate consumma-

AL-NAJIM ET AL.
tory behavior (122). When rats are exposed to a flavored (97, 129, 166, 184, 325). However, if we plot a trend in
solution like sucrose, which does not induce negative con- those studies, we can see that humans and rats did not
sequences, they develop a “liking” of the solution. How- completely avoid the food provided to them which indicates
ever, if the sucrose solution is then paired with a drug that that they may still “like” sweet and fatty food but they
induces nausea, they will feel endangered and develop a “avoid” eating the same quantity as they did before the
taste aversion to the same solution. This is expressed by operation, possibly in an attempt to avoid negative visceral
conditioned disgust reactions such as mouth gaping (221). signals associated with larger quantities. Therefore, they are
On the other hand, if taste avoidance occurs, then the ani- more likely to have developed conditioned taste avoidance.
mal may still like the food and choose it over others but tries A study comparing intake of high-fat diets after RYGB in
to avoid large quantities of it. In further tests, Suncus mu- rats that were either exposed or not exposed to the same
rinus (house musk shrew) were tested with a sucrose solu- high-fat diet before surgery suggest that if the high-fat diet
tion paired with amphetamine, cocaine, or morphine. The was novel, then the rats completely avoided subsequent
shrew showed positive, euphoric reactions to solutions. intake when the high-fat diet was presented after surgery.
However, they reacted to the change in their physiological However, if the rats were familiar with the high-fat diet
state as a sign of danger and thus avoided approaching these before surgery, they again consumed the diet after surgery,
solutions. The shrew yet preferred the solution that it had but quickly reduced the total consumption to much lower
taste avoidance towards rather than the other solution it levels. The rats however never stopped consuming the high-
had a learned taste aversion towards (221, 222, 279). fat diet, suggesting that the palatability did not change but
rather they became conditioned to avoid larger quantities
During the early phase after bariatric surgery, patients suf- (265).
fer from a number of symptoms associated with eating that
can be grouped under an umbrella term of “postprandial
discomfort.” Postprandial discomfort may have a signifi- VII. CONCLUSION AND PERSPECTIVES
cant impact on conditioned eating behavior including food
choices, portion size, frequency of food consumption, meal Weight loss following bariatric surgery is a result of reduced
times, and so on. calorie intake. Altered satiety, food reward, and food pref-
erences may all contribute to the reduction in calorie intake.
2. Postprandial discomfort None of those eating behavior entities works in isolation.
Instead, they interact in the same individual and have addi-
Postprandial discomfort refers to a number of symptoms tive or synergistic effects as a consequence of conditioned
that can occur individually or collectively after an eating and/or unconditioned factors. However, bariatric surgery
episode. Those symptoms include abdominal pain, diar- procedures still have risks, and not all obese patients are
rhea, borborygmi, nausea, bloating, fatigue, a desire to lie eligible or indeed want surgery. Therefore, understanding
down after meals, facial flushing, palpitations, perspiration the mechanisms of successful therapies such as bariatric
tachycardia, hypotension, syncope, and hypoglycemia surgery may help improve other treatment options for obe-
(297). Most research studies focus on Dumping Syndrome sity. In addition, a number of patients after bariatric surgery
(DS) as the main cause of postprandial discomfort. The have suboptimal weight loss. Understanding how these pa-
rapid absorption of simple carbohydrates causes an ele- tients differ from those that lose more weight especially as
vated production of insulin, which in turn lead to a signifi- regards eating behavior may help make the surgical treat-
cant reduction in blood sugar glucose and hypoglycemia. ments even more successful.
Changing the diet to a high-protein, low gastrointestinal
diet can prevent the symptoms of DS in the majority of The future is likely to see more combined gut hormone
patients. However, we cannot disregard certain eating hab- therapies (299), minimally invasive devices such as the En-
its, for example, eating large amount of food or fast eating doBarrier (170), or even a combined multi-model “medical
pace, in resulting with increased postprandial production of bypass” approach (195), on appetite and food preferences.
satiety peripheral signals and therefore negative visceral sig- These treatments can mimic various components of the
nals being sent to the brain. RYGB and could collectively help us guide perspective stud-
ies and treatments in the right direction. The challenge will
Postprandial discomfort often occurs after the consumption remain in finding out whether these minimally invasive
of high carbohydrates and fatty meals (91). It was originally treatments are ultimately capable of shifting or “resetting”
thought that because the brain associates those food groups the body’s fat “set point” similarly to RYGB.
with sickness, a conditioned taste aversion to “sweet” and
“fatty” food occurs. Sclafani and Koopmans (261) were the ACKNOWLEDGMENTS
first researchers to report that a jejunoileal bypass surgery in
rats produces a strong and persistent conditioned taste aver- We acknowledge the work done by Ghalia Abdeen on VSG
sion to novel-flavored solutions. Extensive research in this adolescents in Saudi Arabia and referenced in the manu-
area over the last few decades supported that hypothesis script as unpublished work.

Address for reprint requests and other correspondence: C. 15. Bala V, Rajagopal S, Kumar DP, Nalli AD, Mahavadi S, Sanyal AJ, Grider JR, Murthy KS.
Release of GLP-1 and PYY in response to the activation of G protein-coupled bile acid
le Roux, Diabetes Complications Research Centre, UCD receptor TGR5 is mediated by Epac/PLC-␧ pathway and modulated by endogenous
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No conflicts of interest, financial or otherwise, are declared
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2018 PHYS REV Ingestão Alimentar e Comportamento Alimentar Depois de Cirurgia Bariátrica

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Physiol Rev 98: 1113–1141, 2018

Published May 2, 2018; doi:10.1152/physrev.00021.2017

FOOD INTAKE AND EATING BEHAVIOR AFTER

Satiety is the state in which the hunger drive, and conse-

Obesity has been declared a chronic disease by a number of

0031-9333/18 Copyright © 2018 the American Physiological Society 1113

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Other prandial and postprandial signals are also generated

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Pre-prandial motivation Satiation Satiety

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compared with presurgery (163), which supports the no- C. Frequency

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Furthermore, when rats after RYGB were presented with a

A. Mechanisms That Explain Reduction in

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Table 1. Summary of the effect of appetite neurotransmitters on changes in food preferences

Reference numbers are given in parentheses.

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Table 2. Summary of the effect of appetite hormones on changes in food preferences

Reference numbers are given in parentheses.

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Psychological traits, cognition,

mains of taste (stimulus identification, ingestive motiva-

tion, and digestive preparation) in eating behavior.

Black arrows represent triggers of eating behavior,

glycemic excursions, satiation) dimensions. Any change

to one or all of the stimulus identification, ingestive

motivation, and digestive preparation domains can also

alter eating behavior and thus obesity.

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