Obesity Surgery

, Volume 22, Issue 10, pp 1648–1657

Gut Hormones and Leptin: Impact on Energy Control and Changes After Bariatric Surgery—What the Future Holds


    • Barts and the London School of Medicine
    • Barts and the London Hospital
  • Carel le Roux
    • Experimetal Pathology, Conway Institute, School of Medicine and Medical SciencesUniversity College Dublin

DOI: 10.1007/s11695-012-0698-9

Cite this article as:
Michalakis, K. & le Roux, C. OBES SURG (2012) 22: 1648. doi:10.1007/s11695-012-0698-9


Obesity is now considered the new world epidemic. In an attempt to face this menace to public health, several treatments, apart from the traditional nutritional modification and oral medication, have been introduced, among them bariatric surgery and gut hormone-based treatments. The gastrointestinal (GI) tract is a powerful endocrine organ, releasing active peptides and influencing appetite and glycaemic control. Alteration of the GI tract, in ways that exaggerate the secretion and levels of the gut hormones, creates a new functional equilibrium that further contributes to weight loss. The purpose of this review is to explore the mechanisms that drive this gut hormone-derived body regulation, as well as the changes that occur to them after bariatric surgery. Close to that, leptin, a hormone secreted by adipose tissue will be analysed, as its pathways are closely related to those of the gut hormones. Gut hormones are strongly implicated in energy control, and various effects of bariatric surgery in weight loss are directly related to the alteration of the levels of these hormones.


Gut peptidesBariatric surgeryEnergy control



Agouti-related peptide


AMP-activated protein kinase


Arcuate nucleus


Alpha-melanocyte-stimulating hormone


Body mass index


Central nervous system


Cocaine- and amphetamine-regulated transcript


Dipeptidyl peptidase-4


Growth hormone secretagogue receptor


Glucose-dependent insulinotropic peptide


Glucagon-like peptide-1


Glycated haemoglobin


Homeostasis assessment model of insulin resistance


Neuropeptide Y


Nucleus of the solitary tract






Pancreatic polypeptide


Paraventricular nucleus


Peptide YY(3–36)


Roux-en-Y gastric bypass


Traditional treatment of obesity includes either lifestyle modification combined with oral medication, or—if certain eligibility criteria are fulfilled—surgical procedures that act in various ways. Bariatric surgery can be broadly classified as stomach only procedures (gastric banding, vertical banded gastroplasty—not existing any more—and sleeve gastrectomy) that alter the anatomy of the stomach and food passage through the stomach, small bowel only procedures (duodenal exclusion) which aimed to create a shorter small bowel resulting in calorie malabsorption and combination procedures of the stomach and small bowel (Roux-en-Y gastric bypass, biliopancreatic diversion and duodenal switch) that combine the benefits of the two previous procedures (Fig. 1). The traditional belief that bariatric surgery acts only by limiting the space for food consumption or diminishing the absorption of nutrients seems to be enriched by new theories that strongly support the implication of gut hormones in weight loss, an implication that becomes stronger after the modification of the gastrointestinal (GI) tract.
Fig. 1

Major operations used in bariatric surgery. Blue represents normal GI tract existing before operation and purple represents the resulting GI tract after each type of bypass (post-surgery)

Central Regulation of Appetite and Energy Homeostasis

The brain translates multiple peripheral and neural signals to control the regulation of energy homeostasis, maintaining a balance between food intake and energy expenditure. The arcuate nucleus (ARC) of the hypothalamus integrates most of the energy homeostatic feedback mechanisms [1]. Both short- and long-term hormonal and nutrient signals from the periphery interact with neuronal feedback from the NTS. All signals are transmitted to two neuronal groups, one acting as orexigenic (appetite stimulating) via agouti-related peptide (AgRP) and neuropeptide Y (NPY) neurotransmitters, and the other counteracting those actions promoting anorexigenic properties mainly motivated by CART and pro-opiomelanocortin (POMC) neurotransmitters. Both neuronal populations innervate the PVN, which, in turn, sends signals to other areas of the brain, which further regulate overall body homeostasis (Fig. 2).
Fig. 2

Peripheral and central regulation of appetite. GI gastrointestinal tract, PYY peptide YY, POMC pro-opiomelanocortin, AgRP agouti-related peptide, CART cocaine- and amphetamine-regulated transcript, GLP-1 glucagon-like peptide-1, GIP glucose-dependent insulinotropic peptide, NPY neuropeptide Y, OXM oxyntomodulin

Peripheral factors can be divided into those that regulate long-term energy status and are produced by adipose tissue (leptin, adiponectin) and the pancreas (insulin) and those that deal with near-term energy status, such as the hunger signal ghrelin (produced in the stomach), and the gut hormones peptide YY(3–36) (PYY(3–36)), PP, amylin and oxyntomodulin (OXM). The incretin hormones glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and potentially OXM improve the response of the endocrine pancreas to secrete insulin [1].

Although this review mainly focuses on hormones derived from the GI tract and their regulation in appetite, specific mentioning has to be provided regarding leptin. Despite leptin being a product of the adipose tissue, years of research have linked leptin with the main modulators and signals that affect appetite. Leptin is very closely related to the brain regulation of appetite. The way that leptin affects many of the signalling pathways regarding energy expenditure makes it a strong part of the gut hormone effect, though not initially deriving from the gut, but very actively affecting the same pathways that gut hormones do.


Leptin (origin from the Greek word leptos for lean) is a 16-kDa, nonglycosylated peptide of 146 amino acids [2]. Leptin is encoded from the OB gene, that is mainly expressed in adipose tissue (mainly white, to a lesser extend brown), whereas lower levels are also expressed in the hypothalamus, pituitary, gastric epithelium, placenta, mammary glands and gonads [3]. Leptin’s effects are mediated through six types of receptors (secretory ObRe, long-ObRb and short forms—ObRa, c, d, e and f); Re accounts for most of leptin’s binding capacity [4].

Leptin is involved in the regulation of food intake and energy expenditure, storage of fat and insulin signalling [5]. Initially thought to be the treatment of obesity, leptin-deficient mice (ob/ob) and humans were treated with exogenous leptin, but obese humans were leptin resistant with very little weight loss response [6].

Leptin regulates human energy physiology in two ways. When body weight is steady reflecting a balance between expenditure and intake, leptin levels are an indicator of body fat mass. The more important role of leptin may be during weight loss or excessive weight gain, when leptin signals an energy imbalance [7]. It seems that the traditional belief that leptin is the alarm for the body to reduce weight and stop eating is still valid, but more important is the role of leptin in adapting the organism in the state of reduced energy intake and reduced body fat stores [8]. When food restriction occurs, leptin decreases more and disproportionately to body weight reduction, in order to signal the increased need for energy [8].

Leptin is not stable throughout the day with peaks and troughs mainly following the meals. Morning peak is between 10 and 12 a.m. and nocturnal peak appears after midnight, but no clear diurnal pattern is present. Leptin levels are low during fasting and increase several hours after food intake [911].

Leptin seems to exert a crucial role in energy expenditure and regulation of fat mass and body weight [12], its secretion being proportionate to the fat stores of the body. The more an individual gains weight, the more leptin is secreted (together with insulin) leading to an inhibitory circuit to the hypothalamus, which in turn reduces appetite and food consumption and increases energy expenditure and sympathetic tone [13]. On the contrary, starvation and food deprivation reduce leptin levels and increase appetite and parasympathetic tone, preserving energy expenditure at the same time. Leptin has been related to appetite, as well, with studies showing that decreased leptin induced hunger [14] and exogenous leptin reduced desire for food [15]. Nevertheless, a tendency in species to develop leptin resistance through chronic overfeeding is demonstrated by high leptin levels in obese humans and animals [16].

Leptin inhibits food intake and activates thermogenesis [8]. Together with insulin, they serve as signals to the brain to regulate energy homeostasis and adiposity, acting to the central nervous system sharing a common pathway through phosphatidyloinositol 3-kinase [17].

Leptin interacts with various neuropeptides and the central nervous system. Neuropeptide Y (NPY) is known to be orexigenic, through stimulation of appetite [18] and leptin suppresses production and secretion of NPY from neurons in the arcuate nucleus [19] by binding to the satiety centre of the ventral medial nucleus of the hypothalamus. Part of this signalling has to do with another orexigenic peptide, the AgRP. Apart from these actions, leptin seems to down-regulate the expression of endocannabinoids, which in other circumstances would increase appetite. Leptin also stimulates neurons that express alpha-melanocyte-stimulating hormone (α-MSH) and cocaine- and amphetamine-regulated transcripts that act by suppressing appetite and food consumption [19].

Leptin has been also related to immunity and inflammation. Leptin deficiency increases susceptibility to infectious and inflammatory stimuli and is associated with a dysregulated cytokine production. Moreover, leptin levels increase acutely during infection and inflammation and may act protectively to the host [20]. Human leptin was found to stimulate proliferation and activation of human circulating monocytes in vitro, promoting the expression of activation markers CD69, CD25, CD38 and CD71, and leptin receptors were found on dendritic cells’ surface, as well as on human polymorphonuclear neutrophils, promoting neutrophil chemotaxis [20].

Overall leptin effects in the central nervous system (CNS) seem to be mediated through sympathetic nervous system activation, whereas insulin sensitivity increase might be mediated through direct and indirect (CNS) effects that activate AMPK and furthermore increase oxidation of fatty acids at the muscle and finally reduce the content of the intramyocellular lipids [21].

Peptide YY

PYY is secreted from entero-endocrine L cells, which are mainly located in the distal part of the gastrointestinal tract. L cells producing PYY are located mainly in the colon and rectum and respond to food consumption by secreting PYY, whereas fasting seems to suppress this secretion [22]. PYY is recognised in two different forms, one is PYY 1–36 and the other is PYY 3–36. PYY 3–36 is the major circulating form, consisted of 34 amino acids and shows high affinity for Y2 receptors and lesser affinity for Y1 and Y5 receptors [23]. Effects of PYY include inhibition of gastric emptying, inhibition of gallbladder contraction and secretion of pancreatic and gastric secretions, while PYY administration increases the absorption of fluids and electrolytes postprandially [24]. Further actions not directly related to appetite control (cardiac output reduction, vasoconstriction, GFR reduction) have been reported [22].

PYY reduces expression of NPY in the arcuate nucleus, as well as the secretion of NPY from the hypothalamus [25]. Although PYY exerts local inhibition in NPY neurons, it can be orexigenic, when administered intracerebroventricullarly, via indirect action on NPY through different receptors [26]. The usual action of PYY is to activate anorectic POMC neurons, thus reducing food consumption in rats [25]. A crucial role in these interactions is mediated through the Y2 neurons, since Y2 knock-out mice do not show any appetite inhibition after PYY administration [26]. Moreover, PYY seems to cause taste avoidance in rodents and nausea in humans, when administered in high doses, although the same anorexic action can be accomplished without adverse effects [25, 27]. Overall, the well recognised postprandial rise of PYY lasting for 1–2 h results in satiety, reduced food intake in aid of digestion and absorption. PYY levels after a meal correlate with the caloric load and to the composition of the meal [28, 29].

PYY knock-out mice are obese, and PYY administration reversed their phenotype to normal [25, 30]. Obese individuals have lower levels of fasting and postprandial PYY levels that give less and weaker inhibition signal for food consumption [22]. Moreover, obese individuals do not show any resistance to exogenous PYY administration [25].


Ghrelin is a 28 amino acid gut peptide derived from pre-proghrelin. It is produced predominantly from the stomach (66–75 % of total) [31] and pituitary gland [32], whereas the small intestine produces a small amount of ghrelin [33]. Ghrelin is a ligand for the growth hormone secretagogue receptor (GHS-R), but its most pivotal role in humans is its relation to appetite; ghrelin though is not essential for growth hormone secretion, but may increase GH pulsatility [34].

Ghrelin’s levels rise with fasting and fall after a meal [35], resembling the usual daily pattern of eating. Ghrelin is released both centrally, from the pituitary, and peripherally, from the stomach [23]. As for the central actions, it seems to act via the CNS pathways, especially the ARC. Expression has been shown in neurons close to the third cerebral ventricle, hypothalamic nuclei and the mesolimbic dopaminergic system, and intra-CNS ghrelin injection activated arcuate NPY/agouti-related peptide neurons [36, 37], causing increased appetite, whereas NPY/AgRP knock-out mice lacked orexigenic response to ghrelin administration [38].

Carbohydrates and proteins exert a stronger action on ghrelin suppression than fat [39, 40]. When someone accounts for ghrelin’s potential to inhibit the sympathetic nervous system and stimulate adipogenesis, while at the same time reducing adipocyte apoptosis [22], ghrelin’s long-term effects on metabolism and weight seem to lead to weight gain and a shift from fatty acid oxidation to lipolysis [22].

Ghrelin levels are low in obese subjects, higher in lean and very high in cachectic patients (reflecting the different need for food consumption, respectively) [41]. Ghrelin resistance does not exists in the obese, as peripheral administration does stimulate their appetite, but the expected postprandial drop of ghrelin is blunted in obese patients, possibly preventing them from slowing down their eating [41]. On the other hand, patients suffering from anorexia nervosa exhibited increased plasma levels of obestatin, acyl ghrelin and des-acyl ghrelin compared with control subjects.

It is noteworthy that ghrelin measurements and studies recently refer to the “ghrelin system”, that is a spectrum of different ghrelin gene products (acyl ghrelin, des-acyl ghrelin, obestatin, GHS-R and GOAT) [42]. They all form different pieces of the same puzzle. Acyl ghrelin stimulates GH secretion and is also involved in energy homeostasis by promoting food intake and adiposity through a GH-independent mechanism, whereas acyl ghrelin seems to be deactivated by des-acyl ghrelin, which results in a compromise in the functional significance of circulating acyl ghrelin [43]. These on the whole constitute the centre of an integrated gut–brain energy axis, modulating appetite, digestion, gut motility, adiposity and energy partition.


OXM is a peptide released after meals, as a product of the preproglucagon gene. OXM acts through the GLP-1 receptor; both OXM and GLP-1 seem to induce similar neuronal activations, but the affinity of OXM to the GLP-1 receptor is lower [44]. OXM is a 37 amino acid peptide that shares the 29 amino acids with glucagon, while both are released from L cells in response to nutrient ingestion, thus signalling for satiety [22]. Nevertheless, OXM N-terminal amino acid residues are vulnerable to rapid cleavage by dipeptidyl peptidase-4 (DPP4), limiting the inhibition of food intake induced by OXM [45].

When OXM is administered in rats [46], centrally or peripherally, it induces weight loss, whereas similar results have been obtained in humans, only after IV administration in supraphysiological doses [47]. OXM reduces weight, increases satiety, reduces body fat and increases energy expenditure [45, 48]. Moreover, OXM’s anorectic effect is enhanced by OXM-mediated suppression of ghrelin levels (15–20 % in rodents and 44 % in humans) [46, 47], possibly meaning that part of ghrelin’s action is due to the presence of OXM.

Glucose-Dependent Insulinotropic Peptide

Glucose-dependent insulinotropic peptide is an incretin and a 42 amino acid peptide. GIP is secreted from K cells in the duodenum and proximal jejunum. Its release is proportionate to the content of the food and occurs within minutes of ingestion [49]. Whereas GIP does not seem to affect food intake acutely, GIP levels are increased in obese patients [23] and promote energy storage. GIP seems to exert lipolytic actions as well as anabolic actions on adipocytes [50, 51], while at the same time observations in knock-out mice show reduced adipocyte mass and a relevant resistance to fat accumulation, despite a high fat diet [52].

Glucagon-Like Peptide-1

GLP-1 is another incretin secreted from the same endocrine L cells that secrete PYY [53]. L cells are mainly located in the distal ileum and colon and secrete GLP-1 mainly as a response in energy intake. GLP-1 regulates appetite via various mechanisms, which at the end promote satiety. One could divide the actions of GLP-1 according to the site of action that synergistically add to satiety. Initially, gastric emptying is delayed and gastric acid secretion is inhibited [54, 55]; secondly, enhanced insulin release and reduced glucagon secretion follow [54, 55], while also affecting the CNS to reduce food intake and inducing satiety, indirectly via POMC stimulation.

Given the proven actions of GLP-1 on satiety and relevant pathways, many ongoing studies have examined its potential as medication in terms of obesity and/or diabetes. Exogenous GLP-1 administration reduces appetite and energy consumption both in normal and obese individuals [56, 57]. Both intracerebroventricular and paraventricular administration of GLP-1 result in reduced caloric intake in animals [58], while peripheral GLP-1 injection inhibits food intake in rodents and humans [22]. Obese individuals show reduced GLP-1 levels that seem to be restored to normal after weight loss [59].

Protein is not a good driver for GLP-1 levels, while carbohydrates induce GLP-1 increases within 30 min and fat after 2.5 h [60]. GLP-1 levels increase by 4–20-fold after meal consumption [60]. GLP-1 reduces muscle utilisation of glucose, in order for glucose to be available for storage in the liver for future use during fasting [61]. This action is mediated via GLP-1-induced reduction in arterial blood flow, which results in decreased glucose utilisation [61].

Gut Hormones—Changes After Operation

Increased GLP-1 is one of the mechanisms by which Roux-en-Y gastric bypass (RYGB) induces weight loss [29, 6265]. Patients that had undergone surgery showed higher GLP-1 levels than non-operated control subjects of the same weight. Moreover, RYGB patients after weight loss still had higher levels of non-operated matched normal weight controls [66]. Not all of the literature is consistent and it cannot be excluded that the precision of assays at lower levels or the fact that only fasting values were analysed may have played a role [6769]; however, studies that examined postprandial responses showed higher levels after surgery. Patients after RYGB showed higher levels of GLP-1 than those of patients that underwent gastric banding [64, 66], regardless of the final weight and patients after RYGB had higher levels of GLP-1 than those losing a comparable amount of weight through diet [65] (Table 1).
Table 1

Actions of gut hormones and leptin before and after RYGB (abbreviations provided in text)



Change after RYGB


– Signals the increased need for energy [8]

– Debatable levels after RYGB

– Secretion proportionate to the fat stores of the body [12]

− Most studies find a correlation with body fat, body weight or BMI, after surgery [78, 79, 98]

– Suppresses production and secretion of NPY from neurons in the arcuate nucleus [19]

– Down-regulates the expression of endocannabinoids [19]

- Stimulates neurons that express α-melanocyte [19]

– Stimulates hormone (α-MSH) and cocaine- and amphetamine-regulated transcripts [20]


– Inhibits of gastric emptying [24]

– Levels after meal are increased after surgery compared to any of the weight control groups (lean, overweight, obese) [29, 38, 64, 66, 72]

– Inhibits gallbladder contraction and secretion of pancreatic and gastric secretions [24]

– Levels are increased more than with other types of surgery [73]

– Reduces expression of NPY in the arcuate nucleus [25]

– Reduces the secretion of NPY from the hypothalamus [25]

– Rises postprandially


– Levels rise with fasting and fall after a meal [35]

– Levels reduced after RYGB [43]

– Ghrelin injection activates arcuate NPY/agouti-related peptide neurons [36, 37], causing increased appetite

– Gastric banding or partial gastrectomy without the RYGB construction does not lower ghrelin levels [44]

– NPY/AgRP knock-out mice lacked orexigenic response to ghrelin administration [38]


– Reduces weight, increases satiety, reduces body fat


– Increases energy expenditure [45, 48]

– OXM’s anorectic effect is enhanced by OXM-mediated suppression of ghrelin levels [46, 47]


– Increased levels in obese patients [23]


– Promotes energy storage

– Lipolytic actions

– Anabolic actions on adipocytes [50, 51]


– Delays gastric emptying and inhibits gastric acid secretion [54, 55]

– Increased levels after RYGB

– Enhances insulin release and reduces glucagon secretion [54, 55]

– Higher levels than patients with banding

– Reduces food intake and induces satiety indirectly via POMC stimulation

– Higher levels than patients with low calorie diet [6466]

PYY levels increase after RYGB within 2 days [70] and last up to 24 months [71] after the operation. PYY after meal are increased after surgery compared to any of the weight control groups (lean, overweight, obese) [29, 38, 64, 66, 72]. PYY levels were higher in patients that underwent RYGB when compared to other types of bariatric surgery [73].

Ghrelin has been characterised as the hormone that “mirrors” hunger. Initial studies suggested that ghrelin levels were much reduced after RYGB [43], since the part of the stomach that secretes this hormone was removed. Gastric banding or partial gastrectomy without the RYGB construction does not lower ghrelin levels [44]. The signalling of ghrelin that induces hunger may be attenuated in vagotomised patients [74], a fact that explains increased ghrelin after Roux-en-Y surgery, as Sundbom et al. [75] clearly show in their study. A controversy about the physiological role of postoperative ghrelin levels still remains.

Leptin levels have not been universally found to be lower in patients after RYGB [7, 64, 76, 77], but most studies find a correlation with body fat, body weight or body mass index (BMI) after surgery [78, 79]. Recent evidence suggests that—as far as it concerns different types of surgery—sleeve gastrectomy (which appears as a rather promising procedure) causes similar changes in leptin as those produced by RYGB.

Changes in Glucose Homeostasis After RYGB

One of the major indications for RYGB is for the treatment of diabetes mellitus. Remission of diabetes after RYGB can occur within the first few postoperative days [80]. The mechanisms which may be involved include alterations to the upper gut. Some authors have suggested that duodenum bypass contributes to a decrease in an anti-incretin substance that normally would oppose the K cell-derived GIP, while others have suggested that the lower gut and the increased GLP-1 secretion from the L cells play an important role [69, 81, 82]. GLP-1 and PYY are also major mediators of appetite suppression after surgery [70], as both their levels increase post-RYGB, a finding further confirmed by Holdstock et al. [83].

Diabetes in obesity is fundamentally driven by insulin resistance and the effect of surgery on this amelioration and the time it may take to become apparent is controversial. Falkén et al. [84] tried to relate all the proven gut changes to insulin resistance, homeostasis assessment model of insulin resistance (HOMA-IR) and glucose control. They showed that fasting glucose levels did decrease as soon as day 3 postoperatively and that HOMA-IR model values lowered up to 2 months after surgery. Insulin and glucose levels were lower, while at the same time GLP-1 values did increase progressively. Considering that HOMA-IR is an indicator of hepatic insulin resistance and not peripheral insulin resistance [85] and given the dramatic reduction in HOMA-IR values soon after the operation, one could assume that apart from the anti-incretin theory (a state reversed post-surgically that actually helps in mediating insulin secretion in a glucose-dependent state) the changes in insulin resistance contribute to the amelioration of glycaemia as well. Indeed, immediately after the operation, a marked and progressive reduction in lipid content is observed [86] that has been shown to increase hepatic insulin sensitivity [87].

What the Future Holds

  • Advances in GLP-1 receptor agonists

Given the proven action of GLP-1 receptor agonists on weight loss and appetite restriction, several improved products are being tested. Lixisenatide® is a once-daily regimen currently in phase IIII clinical trials [88]. In an attempt to avoid daily commitment to an injection, Exenatide LAR® (long acting) in the form of a weekly injection showed similar results in terms of weight reduction and glycated haemoglobin (HbA1c) decrease when compared to twice daily exenatide [89]. Similar formulas of weekly injections are developed by several companies, in the form of taspoglutide® and albiglutide® [90, 91], while others are currently developing an oral form of GLP-1 agonist [92]. Although proven useful so far and seemingly promising for the future, and despite the fact that GLP-1 receptor agonists have shown moderate effects on weight loss, at the same time they decrease energy expenditure and thus have a limited potential in weight loss in total. That is the reason adjunct therapy might be useful, which leads in the development of other medication categories (mentioned below).
  • Concurrent glucagon/GLP-1 receptor agonists

OXM (the dual agonist of glucagon and GLP-1 receptor) in the form of injection showed reduction of body weight and appetite in obese and normal populations, with the adjunct effect of increasing the energy expenditure, a feature that GLP-1 analogues lack [45, 48], also improving lipid profiles and glucose metabolism [93]. As one of the main drawbacks of that treatment is the rapid degradation of oxyntomodulin by DPP4 peptidases, a degradation-resistant form was injected into mice and resulted in a much longer half-life and increased beneficial effects [94].
  • Ghrelin antagonists

Ghrelin antagonists showed some hope in experimental models, by reducing food intake and weight [95], while future plans include a ghrelin antagonist combined with an obestatin agonist (obestatin is the preproghrelin posttranslational product that holds strong anti-orexigenic actions) that could shift the orexigenic drive that ghrelin gives to an anorexigenic status, mainly induced by obestatin. Roux-en-Y gastric bypass surgery is associated with a decrease in circulating ghrelin but obestatin levels are relatively preserved, resulting in decreased ghrelin/obestatin ratios that might potentially work towards weight loss preservation or even additional weight loss [95].
  • PYY analogues

When PYY was given to mice, weight loss was achieved, together with a decrease in HbA1c [96]. In humans, reductions in food intake have been achieved, but thus far prolonged use of PYY has not been shown to result in weight loss. Moreover, the fact that PYY injection in humans seems to worsen carbohydrate metabolism by excursions in glucose levels puts the mechanism of action and its effects in a debate for the time being [96].
  • Endobarrier

The Endobarrier gastrointestinal liner is an emerging treatment of mechanically bypassing the duodenum and jejunum. The EndoBarrier Gastrointestinal Liner by GI Dynamics© is a long, thin tube of balloon-like material that is designed to line the intestine, keeping food from touching the intestinal walls as this may alter the activation of hormonal signals that originate in the intestine, thus mimicking the effects of a Roux-en-Y gastric bypass procedure without surgery. The device is inserted into a person’s body endoscopically through the mouth, and the process is reversible. Endoscopically placed and removed, the main indication is improved glycaemic control in patients with diabetes and obesity. In an open label controlled trial of patients after Endobarrier insertion, both excess weight loss and total weight change were significantly higher in the Endobarrier group [97] with lower glucose levels, lower HbA1c and a decrease in medication requirements [100].


Obesity will be a major public health concern and novel approaches in terms of treatment are needed. This new approach is no longer focused on the aesthetic result of weight loss; on the contrary, modern treatment of obesity may include surgery that can alter appetite and food consumption in a multi-factorial way. Various molecules secreted from the GI tract exert their specific roles; after surgery, GLP-1 levels increase, easing the handling of glucose load; PYY levels increase and provide a satiety signal, ghrelin decreases and reduces hunger and leptin levels fall in most studies. The GI tract is no longer considered as a mechanical tube, but as an active and complicated endocrine organ, which if modified correctly, can exert unparalleled control on appetite, metabolism and well-being.

Conflict of interest


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