Satiety Gut Hormone Research Articles

OGC P54 Catastrophic dumping after gastrectomy in a patient with absent pituitary treated with octreotide – case report

Abstract Background Gastrectomy results in a profound change in appetite, satiety and response to food. Most people will adapt and manage to maintain adequate enteral nutrition, however severe symptoms can hamper quality of life. Early dumping, defined as noxious symptoms occurring within an hour of food, arises due to a combination of vastly increased satiety gut hormone secretion and fluid shifts. Late dumping (reactive hypoglycaemia) occurs due to enhanced post-prandial incretin hormone secretion. We present a case of severe dumping in a patient with absent pituitary treated with the global counter-regulatory hormone octreotide. Methods A 71-year-old patient with absent pituitary underwent total gastrectomy and oesophago-jejunal anastomosis for a greater curve gastric adenocarcinoma. Post-operatively, the patient developed an overall aversion to eating along with significant nausea and vomiting, diarrhoea, abdominal fullness, and tachycardia. Anti-emetics including droperidol, metoclopramide, and haloperidol yielded limited response. NJ feeding also triggered symptoms and was stopped. Parenteral nutrition was the principal source of diet. A trial of a somatostatin analogue, octreotide, resulted in significant improvement of patient symptoms. A dose increase and then conversion to monthly lanreotide was tolerated well resulting in complete resolution of symptoms and no side effects. Results The pituitary gland and hypothalamus are central to regulating appetite and satiety through complex signalling pathways. Hormone signals, including GLP-1, GIP, PYY and ghrelin act on central circuits within the hypothalamus to modulate intake, gastric emptying, and satiety. With an absent pituitary, these hormonal signalling pathways including somatostatin are disrupted. Octreotide therapy likely works through a combination of central suppression of gut hormone signalling as well as peripheral reduction in gut hormone secretion. Conclusions Dumping syndrome is a multifactorial, quality of life limiting consequence of upper GI resection. In patients with altered central appetite control circuitry the symptoms may be so severe as to prevent any enteral intake, including via NJ tube. Interestingly, considering this an endocrinology problem and acting to suppress all hormonal signalling with octreotide had immediate and enduring success in the presented case. This may represent a route for management of patients with significant dumping symptoms and nutritional compromise after gastrectomy or oesophagectomy.

Propionate stimulates the secretion of satiety hormones and reduces acute appetite in a cecal fistula pig model

Short-chain fatty acids (SCFA) can regulate appetite by stimulating the secretion of satiety hormones. However, the impact of short-chain fatty acid propionate on the release of gut satiety hormones and appetite regulation in pigs is not completely understood. In this study, 16 pigs were infused with saline or sodium propionate through a fistula in the caecum during a 28-day experimental period. We characterized the effects of propionate administration on peptide YY (PYY) and glucagon-like peptide 1 (GLP-1) secretion from colonic tissue, and investigated the role of propionate infusion on the expression of appetite-related genes in the colon and hypothalamus. Further, the direct impact of propionate administration on the expression of orexigenic neuropeptide agouti-related protein (AgRP) in hypothalamic N38 cells was also examined. The results showed that intra-cecal infusion of propionate reduced the short-term feed intake (P < 0.05) but not the long-term feed intake in pigs (P > 0.05). Propionate administration stimulated PYY and GLP-1 release from colon tissue in vivo and ex vivo (P < 0.05). It also upregulated PYY expression in the colonic mucosa (P < 0.05). Meanwhile, the GLP-1 and PYY levels in the blood were increased after intra-cecal infusion of propionate at d 28 (P < 0.05). Additionally, intra-cecal infusion of propionate upregulated the mRNA and protein expression of free fatty acid receptor 2/3 (FFAR2/FFAR3) in the colonic mucosa (P < 0.05). Propionate infusion also downregulated the orexigenic AgRP mRNA expression (P < 0.05) and upregulated the anorexigenic cocaine-and amphetamine-regulated transcript (CART) mRNA expression (P = 0.09) in the hypothalamus. Moreover, propionate administration directly downregulated AgRP expression in hypothalamic N38 cells in a dose-dependent manner (P < 0.05). Collectively, these findings demonstrated that cecal propionate stimulated colonic secretion of satiety hormones and suppressed appetite to reduce the short-term feed intake in pigs. This study highlights that microbial-derived propionate exerts an important role in regulating the physical functions of the host.

Exaggerated postprandial GLP-1 secretion following esophagectomy is not associated with gastric emptying and intestinal transit.

Esophagectomy causes postprandial symptoms associated with an exaggerated postprandial gut hormone response. This study aimed to compare the gastrointestinal transit time of patients 1year after esophagectomy with unoperated controls, including its relation to satiety gut hormone release. In this cross-sectional study, consecutive, disease-free patients after esophagectomy with pyloroplasty were compared with unoperated control subjects to assess gastric emptying (GE) and cecal arrival time (CAT). Serial plasma samples were collected before, and for 300minutes after, a mixed-meal challenge. Body composition was assessed, and symptom scores were calculated. Eleven patients 1year post-esophagectomy (age: 62.6 ± 9.8, male: 82%) did not show a significantly different GE pattern compared with 10 control subjects (P = 0.245). Rather, patients could be categorized bimodally as exhibiting either rapid or slow GE relative to controls. Those with rapid GE trended toward a higher postprandial symptom burden (P = 0.084) without higher postprandial glucagon-like peptide-1 (GLP-1) secretion (P = 0.931). CAT was significantly shorter after esophagectomy (P = 0.043) but was not significantly associated with GE, GLP-1 secretion, or symptom burden. Neither early nutrient delivery to the proximal small intestine nor to the colon explains the exaggerated postprandial GLP-1 response after esophagectomy. GE varies significantly in these patients despite consistent pyloric management.

Potential mechanisms of sleeve gastrectomy for reducing weight and improving metabolism in patients with obesity

Obesity is a severe medical problem endangering the health of individuals worldwide. Sleeve gastrectomy (SG), one of the most commonly performed bariatric procedures, has been widely applied to the treatment of such patients. Currently, the potential mechanisms underlying the significant weight loss and metabolic improvement after SG have been well studied. First, and most importantly, by removing a large volume of stomach, the SG directly or indirectly restricts food intake. Then, there are alterations in the absorption and metabolism of both macro- and micronutrients, which may benefit or worsen the patients’ well-being. Another profound change is enhanced secretion of the satiety gut hormone and reduced secretion of the hunger hormone as a consequence of the operation. Additionally, adjustment of gastrointestinal motility, alteration in the gut microbial community, and an inflammatory response were found after surgery. Therefore, the purpose of the present review was focused on such hypotheses and to compile the accumulated facts on the physiologic mechanism of bariatric surgery so that these results can help improve the understanding of how SG produces substantial weight loss and a significant improvement in the metabolism of patients with metabolic syndrome.

Effect of food ingredients on glucagon‐like peptide‐1 secretion in STC‐1 and HuTu‐80 cells

SummaryThis study aims at identifying food ingredients that have potential to enhance satiety and therefore potentially can be used for preventing and treating obesity. To do so, effects of thirteen food ingredients on the secretion of gut satiety hormone glucagon‐like peptide‐1 (GLP‐1) in enteroendocrine STC‐1 and HuTu‐80 cells were investigated. First, the effects of food ingredients on cell viability were investigated. This was done to determine if the individual ingredient affected cell viability, and in case so, to determine the ingredient concentration below which, the cell viability was unaffected. Enzyme‐treated whey protein, palmitic acid, stearic acid, green tea extract, and hesperidin did not affect GLP‐1 secretion. Functional soy protein, fractionated functional soy protein, acetylated monoglyceride, N‐oleoylethanolamine, epigallocatechin‐3‐gallate, hesperetin, rosemary extract, and kale extract increased GLP‐1 secretion in at least one cell line. However, the effects of the eight potent ingredients on GLP‐1 secretion need to be further investigated in vivo.

Peptide YY Mediates the Satiety Effects of the Short Chain Fatty Acid – Butyrate (P08-004-19)

ObjectivesFermentation of fiber in the gut generates short-chain fatty acids (SCFA), such as butyrate, which decrease food intake and promote weight loss in rodent models. SCFA have been shown to enhance secretion of the gut satiety hormone peptide YY (PYY). However, it is unknown whether PYY is causative to SCFA-induced changes in energy balance. Our Objectives were to determine the dose-response effects of butyrate on energy balance, and assess whether PYY signaling is essential for mediating the satiety effects of butyrate. MethodsMale Sprague Dawley rats (8 wks old, n = 39) were randomized to one of three isocaloric (4.63 kcal/g) diets: 1) control (0% sodium butyrate, n = 14), 2) 5% sodium butyrate (n = 13), or 3) 10% sodium butyrate (n = 12), and followed for upto 4 weeks. A PYY Y-2 receptor antagonist (BIIE0246) or vehicle were administered IP acutely during the study. Measurements included food intake, respiratory quotient, and energy expenditure (CLAMS®), and body composition (Minispec LF110 NMR). ResultsCompared to control, 10% sodium butyrate decreased food intake and respiratory quotient for 4 days, whereas, 5% sodium butyrate was ineffective. Notably, compared to control, 10% sodium butyrate decreased body weight and fat gain without changing energy expenditure. Importantly, systemic Y-2 receptor blockade stimulated food intake and increased respiratory quotient, without altering energy expenditure, only in 10% sodium butyrate group. ConclusionsWe found that dietary butyrate dose-dependently decreases food intake and respiratory quotient. Importantly, Y-2 receptor blockade attenuated butyrate-induced hypophagia, which supports a role for endogenous PYY in the satiety effects of dietary butyrate. Funding SourcesNSERC, Heart and Stroke Foundation of Canada.

The PYY/Y2R-Deficient Mouse Responds Normally to High-Fat Diet and Gastric Bypass Surgery.

Background/Goals: The gut hormone peptide YY (PYY) secreted from intestinal L-cells has been implicated in the mechanisms of satiation via Y2-receptor (Y2R) signaling in the brain and periphery and is a major candidate for mediating the beneficial effects of bariatric surgery on appetite and body weight. Methods: Here we assessed the role of Y2R signaling in the response to low- and high-fat diets and its role in the effects of Roux-en-Y gastric bypass (RYGB) surgery on body weight, body composition, food intake, energy expenditure and glucose handling, in global Y2R-deficient (Y2RKO) and wildtype (WT) mice made obese on high-fat diet. Results: Both male and female Y2RKO mice responded normally to low- and high-fat diet in terms of body weight, body composition, fasting levels of glucose and insulin, as well as glucose and insulin tolerance for up to 30 weeks of age. Contrary to expectations, obese Y2RKO mice also responded similarly to RYGB compared to WT mice for up to 20 weeks after surgery, with initial hypophagia, sustained body weight loss, and significant improvements in fasting insulin, glucose tolerance, insulin resistance (HOMA-IR), and liver weight compared to sham-operated mice. Furthermore, non-surgical Y2RKO mice weight-matched to RYGB showed the same improvements in glycemic control as Y2RKO mice with RYGB that were similar to WT mice. Conclusions: PYY signaling through Y2R is not required for the normal appetite-suppressing and body weight-lowering effects of RYGB in this global knockout mouse model. Potential compensatory adaptations of PYY signaling through other receptor subtypes or other gut satiety hormones such as glucagon-like peptide-1 (GLP-1) remain to be investigated.

Attenuation of satiety gut hormones increases appetitive behavior after curative esophagectomy for esophageal cancer

Reduced appetite and weight loss are common after esophagectomy (ES), and this cohort demonstrates an exaggerated postprandial satiety gut hormone response. Satiety gut hormones modulate food reward, resulting in reduced energy intake. This study aimed to determine the effect of satiety gut hormone modulation by measuring the effect of the somatostatin analog octreotide on appetitive behavior among patients after ES. In this randomized, double-blind, placebo-controlled crossover study, patients ≥1 y after ES and matched controls received either 1 mL 0.9% saline or 1 mL (100 μg) octreotide subcutaneously before completing a progressive ratio task. A measure of appetitive behavior, this task requires subjects to undertake progressively increasing amounts of work to obtain a sweet-fat reinforcer; the final completed increment (breakpoint) represents reinforcer reward value. Separate cohorts were studied in the fasted or 1-h postprandial states. Thirty-six subjects (ES, n=18; matched controls, n=18) were studied. The ES subjects were 2.5±0.3 y postoperation and had a weight loss of 14.6%±2.6% and elevated postprandial glucagon-like peptide 1 compared with controls (49.2±13.4 compared with 20.2±2.3 pM; P=0.04). Octreotide did not alter the breakpoint among ES or control subjects when tested in a fasting condition (ES: 980±371 compared with 1700±584 clicks; P=0.16; controls: 1056±274 compared with 1124±273 clicks; P=0.81). When tested 1 h postprandially, octreotide was associated with an increased breakpoint compared with placebo among ES subjects (322±143 compared with 246±149 clicks; P=0.04) but not controls (248±119 compared with 247±120 clicks; P=0.97). Attenuation of the exaggerated postprandial satiety gut hormone response is associated with increased appetitive behavior toward a sweet-fat stimulus among patients post-ES. Suppression of satiety gut hormones may be a novel target to increase appetite, food intake, and body weight among patients after ES. This study was registered at clinicaltrials.gov as NCT02381249.

Role of neurotransmitters 5-hydroxytryptamine and substance P in anorexia induction following oral exposure to the trichothecene T-2 toxin

Trichothecene mycotoxins, a family of common contaminants on cereal grains, are known to negatively impact human and animal health with adverse effect on food consumption being of particular concern. T-2 toxin has been previously demonstrated to induce anorectic response in several animal species including mouse, rat, rabbit. Although the T-2 toxin-induced anorectic response has been associated with the release of gut satiety hormone, much less is known about the role of neurotransmitter in this response. To address this gap, we employed a nocturnal mouse food refusal model to test the hypothesis that neurotransmitters 5-hydroxytryptamine (5-HT) and substance P (SP) mediate anorexia induction by T-2 toxin. Elevations of plasma 5-HT and SP markedly corresponded to anorexia induction following oral exposure to T-2 toxin. Direct administration of exogenous 5-HT and SP induced anorectic responses similar to T-2 toxin. The 5-HT3 receptor (5-HT3R) antagonist granisetron evoked a dose-dependent attenuation of both 5-HT- and T-2 toxin-induced anorectic responses. Pretreatment with neurokinin-1 receptor (NK-1R) antagonist Emend® dose-dependently attenuated both SP- and T-2 toxin-induced anorectic responses. To summarize, the results suggest that both 5-HT and SP play important roles in anorexia induction by T-2 toxin. 5-HT is more potent and long-acting than SP in this response.

PS02.220: ATTENUATION OF SATIETY GUT HORMONES INCREASES APPETITE AFTER CURATIVE ESOPHAGECTOMY FOR ESOPHAGEAL CANCER

Abstract Background Reduced appetite and weight loss after esophagectomy (ES) occur in the context of an exaggerated postprandial satiety gut hormone response. Satiety gut hormones modulate central processing of food reward, resulting in reduced energy intake. The aim of this study was to investigate the effect of satiety gut hormone attenuation using the somatostatin analogue octreotide on appetitive behavior among patients after curative ES. Methods In this randomized, double-blind, placebo-controlled crossover study, disease-free patients at least one year after ES with gastric conduit reconstruction and matched controls received either 1mL 0.9% saline or 1mL (100μg) octreotide subcutaneously, before completing a progressive ratio task (PRT). A measure of appetitive behavior, the PRT requires subjects to undertake progressively increasing amounts of work to obtain a reinforcer—the final completed increment (breakpoint) representing reinforcer reward value in different states. Separate cohorts were studied in the fasted or 1-hour postprandial states. The institutional Research Ethics Committee approved the study (REC 2015/21/02), which was registered on ClinicalTrials.gov prior to recruitment of the first participant (NCT02381249). Results 36 subjects (ES, n = 18, matched controls, n = 18) were studied. 2.5 ± 0.3 years postoperatively, ES patients demonstrated 14.6 ± 2.6% weight loss and an elevated postprandial GLP-1 (49.2 ± 13.4 versus controls with 20.2 ± 2.3 pM, P = 0.038). Octreotide did not alter appetite among ES or control subjects when tested fasting (breakpoint, ES: 980 ± 371 versus 1700 ± 583, P = 0.16; control: 1056 ± 274 versus 1124 ± 273, P = 0.80). When tested one hour postprandially, octreotide was associated with increased appetitive behavior versus placebo among ES subjects (breakpoint, 322 ± 143 versus 246 ± 149, P = 0.037), but not controls (248 ± 119 versus 247 ± 120, P = 0.98). Conclusion Attenuation of the exaggerated postprandial satiety gut hormone response is associated with increased appetitive behavior towards a sweet-fat stimulus among patients post ES. Suppression of satiety gut hormones may represent a novel target to increase appetite, food intake and body weight in patients after esophagectomy. Disclosure All authors have declared no conflicts of interest.

Sensing of L-Arginine by Gut-Expressed Calcium Sensing Receptor Stimulates Gut Satiety Hormones Cholecystokinin and Glucose-Dependent Insulinotropic Peptide Secretion in Pig Model.

Nutrients regulate the secretion of gut satiety hormones, which is related to the modulation of food intake and blood glucose levels. Calcium-sensing receptor (CaSR) is involved in regulating gut hormone secretion in response to l-amino acids and multivalent cations. Rodents are often used to investigate the effect of nutrients on these hormonal release. However, results obtained using rodent models are difficult to be applied in humans, we used pigs as a model in this study because their physiology is similar to that of humans. In this study, we investigated whether l-Arginine (l-Arg) could induce gut hormones cholecystokinin (CCK) and glucose-dependent insulinotropic peptide (GIP) secretion in the porcine duodenum and if so, whether CaSR mediated l-Arg-regulated gut satiety hormone secretion. Our data showed that treatment with 20 and 50 mM l-Arg induced CCK and GIP secretion compared with 0 mM l-Arg. However, treatment with d-Arg (an inactive isomer) failed to elicit this response. The potency of l-Arg to induce CCK and GIP secretion was enhanced in the presence of extracellular Ca2+ and CaSR agonist cinacalcet. However, the effect of Arg on CCK and GIP secretion was attenuated by blocking CaSR and its downstream signaling molecules adenylate cyclase (AC) and phospholipase C (PLC). Taken all together, pig duodenum provides an appropriate model to explore the effects of l-Arg on the secretion of the satiety-related gut hormones CCK and GIP and the role of CaSR in this effect. Further investigations are needed to verify the effect of l-Arg on food intake and blood glucose in human study. PRACTICAL APPLICATION: l-Arginine is able to modulate cholecystokinin and glucose-dependent insulinotropic peptide secretion through the CaSR in pig model, which has a potential role in regulating food intake and blood glucose levels.

Anorectic response to the trichothecene T-2 toxin correspond to plasma elevations of the satiety hormone glucose-dependent insulinotropic polypeptide and peptide YY3-36

T-2 toxin, a potent type A trichothecene mycotoxin, is produced by various Fusarium species and can negatively impact animal and human health. Although anorexia induction is a common hallmark of T-2 toxin-induced toxicity, the underlying mechanisms for this adverse effect are not fully understood. The goal of this study was to determine the roles of two gut satiety hormones, glucose-dependent insulinotropic polypeptide (GIP) and Peptide YY3-36 (PYY3-36) in anorexia induction by T-2 toxin. Elevations of plasma GIP and PYY3-36 markedly corresponded to anorexia induction following oral exposure to T-2 toxin using a nocturnal mouse anorexia model. Direct administration of exogenous GIP and PYY3-36 similarly induced anorectic responses. Furthermore, the GIP receptor antagonist Pro3GIP dose-dependently attenuated both GIP- and T-2 toxin-induced anorectic responses. Pretreatment with NPY2 receptor antagonist JNJ-31020028 induced a dose-dependent attenuation of both PYY3-36- and T-2 toxin-induced anorectic responses. To summarize, these findings suggest that both GIP and PYY3-36 might be critical mediators of anorexia induction by T-2 toxin.

Potential roles for glucagon-like peptide-17–36 amide and cholecystokinin in anorectic response to the trichothecene mycotoxin T-2 toxin

Anorexia is a hallmark of animal and human exposed to T-2 toxin, a most poisonous trichothecene mycotoxins contaminating various cereal grains including wheat, corn and barley. Although this adverse effect has been well characterized in several animal species, the underlying mechanisms are unclear. The goal for this study was to elucidate the roles of two gut satiety hormones, glucagon-like peptide-17–36 amide (GLP-1) and cholecystokinin (CCK) in T-2 toxin-evoked anorectic response using a mouse anorexia bioassay. Elevations of plasma GLP-1 and CCK significantly corresponded to anorexia induction by T-2 toxin. Direct administration of exogenous GLP-1 and CCK markedly evoked anorectic responses similar to T-2 toxin. The GLP-1 receptor (GLP-1R) antagonist Exendin9-39 dose-dependently cause attenuation of both GLP-1- and T-2 toxin-induced anorectic responses. Pretreatment with the CCK1 receptor (CCK1R) antagonist SR 27897 and CCK2 receptor (CCK2R) antagonist L-365,260 attenuated anorexia induction by both CCK- and T-2 toxin in a dose dependent manner. Taken together, our findings suggest that both GLP-1 and CCK play contributory roles in T-2 toxin-induced anorexia.

Gut satiety hormones cholecystokinin and glucagon-like Peptide-17-36 amide mediate anorexia induction by trichothecenes T-2 toxin, HT-2 toxin, diacetoxyscirpenol and neosolaniol

The food-borne trichothecene mycotoxins have been documented to cause human and animal food poisoning. Anorexia is a hallmark of the trichothecene mycotoxins-induced adverse effects. Type B trichothecenes have been previously demonstrated to elicit robust anorectic responses, and this response has been directly linked to secretion of the gut satiety hormones cholecystokinin (CCK) and glucagon-like peptide-17–36 amide (GLP-1). However, less is known about the anorectic effects and underlying mechanisms of the type A trichothecenes, including T-2 toxin (T-2), HT-2 toxin (HT-2), diacetoxyscirpenol (DAS), neosolaniol (NEO). The purpose of this study was to relate type A trichothecenes T-2, HT-2, DAS and NEO-induced anorectic response to changes plasma concentrations of CCK and GLP-1. Following both oral gavage and intraperitoneal (IP) administration of 1mg/kg bw T-2, HT-2, DAS and NEO evoked robust anorectic response and secretion of CCK and GLP-1. Elevations of plasma CCK markedly corresponded to anorexia induction by T-2, HT-2, DAS and NEO. Following oral exposure, plasma CCK was peaked at 6h, 6h, 2h, 2h and lasted up to 24h, 24h, > 6h, > 6h for T-2, HT-2, DAS and NEO, respectively. IP exposed to four toxins all induced elevation of CCK with peak point and duration at 6h and >24h, respectively. In contrast to CCK, GLP-1 was moderately elevated by these toxins. Following both oral and IP exposure, T-2 and HT-2 evoked plasma GLP-1 elevation with peak point and duration at 2h and 6h, respectively. Plasma GLP-1 was peaked at 2h and still increased at 6h for IP and oral administration with DAS and NEO, respectively. In conclusion, CCK plays a contributory role in anorexia induction but GLP-1 might play a lesser role in this response.

Weight Loss, Satiety, and the Postprandial Gut Hormone Response After Esophagectomy: A Prospective Study.

To prospectively characterize changes in body weight, satiety, and postprandial gut hormone profiles following esophagectomy. With improved oncologic outcomes in esophageal cancer, there is an increasing focus on functional status and health-related quality of life in survivorship. Early satiety and weight loss are common after esophagectomy, but the pathophysiology of these phenomena remains poorly understood. In this prospective study, consecutive patients undergoing esophagectomy with gastric conduit reconstruction were studied preoperatively and at 10 days, 6 weeks, and 3 months postoperatively. Glucagon-like peptide 1 (GLP-1) immunoreactivity of plasma collected immediately before and at 15, 30, 60, 90, 120, 150, and 180 minutes after a standardized 400-kcal mixed meal was determined. Gastrointestinal symptom scores were computed using European Organization for Research and Treatment of Cancer questionnaires. Body weight loss at 6 weeks and 3 months postoperatively among 13 patients undergoing esophagectomy was 11.1 ± 2.3% (P < 0.001) and 16.3 ± 2.2% (P < 0.0001), respectively. Early satiety (P = 0.043), gastrointestinal pain and discomfort (P = 0.01), altered taste (P= 0.006), and diarrhea (P= 0.038) scores increased at 3 months postoperatively. Area under the curve for the satiety gut hormone GLP-1 was significantly increased from 10 days postoperatively (2.4 ± 0.2-fold increase, P < 0.01), and GLP-1 peak increased 3.8 ± 0.6-, 4.7 ± 0.8-, and 4.4 ± 0.5-fold at 10 days, 6 weeks, and 3 months postoperatively (all P < 0.0001). Three months postoperatively, GLP-1 area under the curve was associated with early satiety (P = 0.0002, R = 0.74), eating symptoms (P = 0.007, R = 0.54), and trouble enjoying meals (P = 0.0004, R = 0.73). After esophagectomy, patients demonstrate an exaggerated postprandial satiety gut hormone response, which may mediate postoperative changes in satiety, body weight, and gastrointestinal quality of life.

Role of Peptide YY3-36 and Glucose-Dependent Insulinotropic Polypeptide in Anorexia Induction by Trichothecences T-2 Toxin, HT-2 Toxin, Diacetoxyscirpenol, and Neosolaniol.

Trichothecences, secondary metabolites produced by Fusarium, are serious health risks to humans and animals worldwide. Although type A trichothecence-induced food refusal has been observed, the mechanism underlying the anorexia caused by these compounds is not fully understood. In this study, we hypothesized that anorexia induced by type A trichothecenes, including T-2 toxin (T-2), HT-2 toxin (HT-2), diacetoxyscirpenol (DAS), and neosolaniol (NEO), in mice corresponds to the changes in the gut satiety hormones peptide YY3-36 (PYY3-36) and glucose-dependent insulinotropic polypeptide (GIP) in plasma. A well-characterized mouse food refusal model was used in this assay. Oral exposure to or intraperitoneal (ip) injection of 1 mg/kg bw T-2, HT-2, DAS, or NEO resulted in dramatically decreased food intake, and PYY3-36 and GIP concentrations were elevated accordingly. Specifically, the PYY3-36 and GIP concentrations peaked at 2 h following oral exposure to these 4 toxins individually, although the durations were not identical. After ip administration of T-2 or HT-2, PYY3-36 significantly increased within 6 h. However, no significant difference was found in the DAS and NEO groups. The GIP levels peaked within 2, 2, 0.5, and 0.5 h, respectively, and remained increased up to 6, 6, 2, and 6 h, respectively, following T-2, HT-2, DAS, or NEO ip exposure. The increase in GIP was greater than that of PYY3-36 after exposure to the 4 toxins using 2 administration routes. Together, these findings suggest that PYY3-36 and GIP play a role in T-2-, HT-2-, DAS-, and NEO-induced anorexia.

How do patients' clinical phenotype and the physiological mechanisms of the operations impact the choice of bariatric procedure?

Bariatric surgery is currently the most effective option for the treatment of morbid obesity and its associated comorbidities. Recent clinical and experimental findings have challenged the role of mechanical restriction and caloric malabsorption as the main mechanisms for weight loss and health benefits. Instead, other mechanisms including increased levels of satiety gut hormones, altered gut microbiota, changes in bile acid metabolism, and/or energy expenditure have been proposed as explanations for benefits of bariatric surgery. Beside the standard proximal Roux-en-Y gastric bypass and the biliopancreatic diversion with or without duodenal switch, where parts of the small intestine are excluded from contact with nutrients, resectional techniques like the sleeve gastrectomy (SG) have recently been added to the armory of bariatric surgeons. The variation of weight loss and glycemic control is vast between but also within different bariatric operations. We surveyed members of the Swiss Society for the Study of Morbid Obesity and Metabolic Disorders to assess the extent to which the phenotype of patients influences the choice of bariatric procedure. Swiss bariatric surgeons preferred Roux-en-Y gastric bypass and SG for patients with type 2 diabetes mellitus and patients with a body mass index >50 kg/m2, which is consistent with the literature. An SG was preferred in patients with a high anesthetic risk or previous laparotomy. The surgeons’ own experience was a major determinant as there is little evidence in the literature for this approach. Although trends will come and go, evidence-based medicine requires a rigorous examination of the proof to inform clinical practice.

Effect of two bakery products on short-term food intake and gut-hormones in young adults: a pilot study

The aim of this study is to compare the effect of conventional bread and a whole grain bread on appetite and energy intake, satiety and satiety gut-hormones. A randomized controlled crossover pilot study was carried out in 11 university students (age: 18.7 ± 0.9 years; body mass index: 22.7 ± 2.7 kg/m2). Participants consumed two different mid-morning cereal-based snacks, including a conventional or whole grain bread. Two testing days were completed, including satiety questionnaires, blood sampling and consumption of standardized breakfast, mid-morning test-snacks and ad libitum lunch. Several gut-hormones were analysed and satiation was assessed using Visual Analogue Scale scores. The consumption of whole grain bread increased satiety perception, decreased the remained energy intake during the testing day, and decreased the postprandial response of peptide YY, compared with conventional bread (p < 0.005). These data suggest that the consumption of whole grain bread might be a useful strategy to improve satiety.

Link Between Increased Satiety Gut Hormones and Reduced Food Reward After Gastric Bypass Surgery for Obesity.

Context:Roux-en-Y gastric bypass (RYGB) surgery is an effective long-term intervention for weight loss maintenance, reducing appetite, and also food reward, via unclear mechanisms.Objective:To investigate the role of elevated satiety gut hormones after RYGB, we examined food hedonic-reward responses after their acute post-prandial suppression.Design:These were randomized, placebo-controlled, double-blind, crossover experimental medicine studies.Patients:Two groups, more than 5 months after RYGB for obesity (n = 7–11), compared with nonobese controls (n = 10), or patients after gastric banding (BAND) surgery (n = 9) participated in the studies.Intervention:Studies were performed after acute administration of the somatostatin analog octreotide or saline. In one study, patients after RYGB, and nonobese controls, performed a behavioral progressive ratio task for chocolate sweets. In another study, patients after RYGB, and controls after BAND surgery, performed a functional magnetic resonance imaging food picture evaluation task.Main Outcome Measures:Octreotide increased both appetitive food reward (breakpoint) in the progressive ratio task (n = 9), and food appeal (n = 9) and reward system blood oxygen level-dependent signal (n = 7) in the functional magnetic resonance imaging task, in the RYGB group, but not in the control groups.Results:Octreotide suppressed postprandial plasma peptide YY, glucagon-like peptide-1, and fibroblast growth factor-19 after RYGB. The reduction in plasma peptide YY with octreotide positively correlated with the increase in brain reward system blood oxygen level-dependent signal in RYGB/BAND subjects, with a similar trend for glucagon-like peptide-1.Conclusions:Enhanced satiety gut hormone responses after RYGB may be a causative mechanism by which anatomical alterations of the gut in obesity surgery modify behavioral and brain reward responses to food.

Mechanism Underlying the Weight Loss and Complications of Roux-en-Y Gastric Bypass. Review.

Various bariatric surgical procedures are effective at improving health in patients with obesity associated co-morbidities, but the aim of this review is to specifically describe the mechanisms through which Roux-en-Y gastric bypass (RYGB) surgery enables weight loss for obese patients using observations from both human and animal studies. Perhaps most but not all clinicians would agree that the beneficial effects outweigh the harm of RYGB; however, the mechanisms for both the beneficial and deleterious (for example postprandial hypoglycaemia, vitamin deficiency and bone loss) effects are ill understood. The exaggerated release of the satiety gut hormones, such as GLP-1 and PYY, with their central and peripheral effects on food intake has given new insight into the physiological changes that happen after surgery. The initial enthusiasm after the discovery of the role of the gut hormones following RYGB may need to be tempered as the magnitude of the effects of these hormonal responses on weight loss may have been overestimated. The physiological changes after RYGB are unlikely to be due to a single hormone, or single mechanism, but most likely involve complex gut-brain signalling. Understanding the mechanisms involved with the beneficial and deleterious effects of RYGB will speed up the development of effective, cheaper and safer surgical and non-surgical treatments for obesity.