peptide-yy and Weight-Loss

Developing novel foods to suppress energy intake and promote negative energy balance and weight loss has been a long-term but commonly unsuccessful challenge. Targeting regulation of appetite is of interest to public health researchers and industry in the quest to develop 'functional' foods, but poor understanding of the underpinning mechanisms regulating food intake has hampered progress. The gastrointestinal (GI) or 'satiety' peptides including cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) secreted following a meal, have long been purported as predictive biomarkers of appetite response, including food intake. Whilst peptide infusion drives a clear change in hunger/fullness and eating behaviour, inducing GI-peptide secretion through diet may not, possibly due to modest effects of single meals on peptide levels. We conducted a review of 70 dietary preload (DIET) and peptide infusion (INFUSION) studies in lean healthy adults that reported outcomes of CCK, GLP-1 and PYY. DIET studies were acute preload interventions. INFUSION studies showed that minimum increase required to suppress ad libitum energy intake for CCK, GLP-1 and PYY was 3.6-, 4.0- and 3.1-fold, respectively, achieved through DIET in only 29%, 0% and 8% of interventions. Whether circulating 'thresholds' of peptide concentration likely required for behavioural change can be achieved through diet is questionable. As yet, no individual or group of peptides can be measured in blood to reliably predict feelings of hunger and food intake. Developing foods that successfully target enhanced secretion of GI-origin 'satiety' peptides for weight loss remains a significant challenge.

Topics: Anti-Obesity Agents; Appetite Regulation; Cholecystokinin; Eating; Energy Metabolism; Feeding Behavior; Female; Glucagon-Like Peptide 1; Humans; Infusions, Parenteral; Male; Peptide Hormones; Peptide YY; Satiety Response; Signal Transduction; Weight Loss

Obesity is a multifactorial, chronic disease that has proven difficult to treat. An increased understanding of aetiological mechanisms is critical to the development of more effective obesity prevention and treatment strategies. A growing body of empirical evidence has demonstrated parallels between obesity, overeating and substance abuse, including shared behavioural, psychological and neurophysiological factors implicated in the excessive intake of both food and substances of abuse. Several different lines of research have recently emerged that hold the potential to shed light on the connection between obesity, food reward and addiction, with studies examining changes in alcohol use/misuse after weight loss surgery providing a particularly interesting perspective on these interrelationships. However, these lines of investigation have proceeded in relative isolation, and relevant research findings have yet to be integrated in a synthesized, comprehensive manner. To provide an opportunity to achieve such a synthesis, a scientific symposium was convened at the Radcliffe Institute in Cambridge, Massachusetts. Invited participants were researchers working in diverse domains related to the intersection between obesity and addiction. Extensive discussion was generated suggesting novel research directions. In this article, we summarize and synthesize the symposium participants' ongoing research in this area, incorporating additional relevant research holding potential clues regarding the connections between obesity, weight loss surgery and addiction.

Topics: Alcohol Drinking; Alcoholism; Animals; Bariatric Surgery; Behavior, Addictive; Ethanol; Gastric Bypass; Glucagon-Like Peptide 1; Humans; Hyperphagia; Obesity; Peptide YY; Reward; Weight Loss

The aims of this article were to review the discrepancy between numbers of people requiring weight loss treatment and results and to assess the potential effects of pharmacologic treatments (recently approved for obesity) and endoscopically deployed devices on quantitative GI traits in development for obesity treatment.. We conducted a review of relevant literature to achieve our objectives.. The 2013 guidelines increased the number of adults recommended for weight loss treatment by 20.9% (116.0 million to 140.2 million). There is an imbalance between efficacy and costs of commercial weight loss programs and drug therapy (average weight loss about 5 kg). The number of bariatric procedures performed in the United States has doubled in the past decade. The efficacy of bariatric surgery is attributed to reduction in the volume of the stomach, nutrient malabsorption with some types of surgery, increased postprandial incretin responses, and activation of farnesoid X receptor mechanisms. These GI and behavioral traits identify sub-phenotypes of obesity, based on recent research.. The mechanisms or traits targeted by drug and device treatments include centrally mediated alterations of appetite or satiation, diversion of nutrients, and alteration of stomach capacity, gastric emptying, or incretin hormones. Future treatment may be individualized based on quantitative GI and behavioral traits measured in obese patients.

Topics: Anti-Obesity Agents; Bariatric Surgery; Combined Modality Therapy; Depression; Endoscopy, Gastrointestinal; Equipment and Supplies; Feeding Behavior; Gastric Balloon; Gastric Bypass; Gastric Emptying; Gastroplasty; Glucagon-Like Peptide 1; Humans; Hypothalamus; Obesity; Organ Size; Peptide YY; Precision Medicine; Principal Component Analysis; Satiation; Stomach; Treatment Outcome; Weight Loss

During childhood and adolescence, a number of factors, including age, puberty, sex, race, and body composition, may contribute to differences in satiety, food intake, and appetite-related peptides. These peptides include the orexigenic peptide ghrelin and anorexigenic gut peptides peptide YY (PYY) and glucagon-like peptide-1 (GLP-1). For example, lower fasting ghrelin levels, lower postprandial ghrelin suppression, and blunted PYY and GLP-1 responses to food intake could contribute to a dysregulation of appetite in already obese children and adolescents. Whereas, changes in these peptides observed during puberty could facilitate growth. A greater understanding of the major moderating factors of appetite-related peptides in the pediatric population is essential to improve interpretation of study findings and for effective tailoring of strategies targeting appetite control to individuals. While more studies are needed, there is some evidence to suggest that exercise-based lifestyle interventions could be a potential therapeutic strategy to improve appetite-peptide profiles in overweight and obese children and adolescents. The aim of this review is (i) to discuss the potential moderating factors of ghrelin, PYY, and GLP-1, including age and puberty, sex, race and body composition; and (ii) to examine the effects of exercise interventions on these appetite-related gut peptides in children and adolescents.

Topics: Adolescent; Adolescent Behavior; Adolescent Development; Age Factors; Appetite Regulation; Body Composition; Child; Child Behavior; Child Development; Eating; Exercise; Exercise Therapy; Female; Ghrelin; Glucagon-Like Peptide 1; Humans; Male; Pediatric Obesity; Peptide YY; Puberty; Risk Factors; Risk Reduction Behavior; Signal Transduction; Treatment Outcome; Weight Loss

Although the role of peptide YY (PYY) as a regulator of energy homeostasis was first highlighted only in 2002, our understanding of the physiological role of PYY has since rapidly advanced. In recent years, insights from mechanistic studies in patients undergoing bariatric surgery, from pancreatic islet research, from functional neuroimaging studies, and from exercise research have greatly added to the field, and these areas provide the focus of discussion for this narrative review. We critically discuss recent findings relating to the role of PYY in mediating the beneficial effects of bariatric surgery, the role of PYY in glucose homeostasis, the role of hepatoportal PYY in mediating its central physiological effects, the specific modulation of brain regions by PYY, and the exercise-induced PYY response.

Topics: Adult; Animals; Bariatric Surgery; Energy Metabolism; Exercise; Female; Glucose; Homeostasis; Humans; Male; Obesity; Peptide YY; Weight Loss

Bariatric surgery has emerged as the most durably effective treatment of type 2 diabetes (DM). However, the mechanisms governing improvement in glucose homeostasis have yet to be fully elucidated. In this review we discuss the various types of surgical interventions and the multitude of factors that potentially mediate the effects on glycemia, such as altered delivery of nutrients to the distal ileum, duodenal exclusion, gut hormone changes, bile acid reabsorption, and amino acid metabolism. Accumulating evidence that some of these changes seem to be independent of weight loss questions the rationale of using body mass index as the major indication for surgery in diabetic patients. Understanding the complex mechanisms and interactions underlying improved glycemic control could lead to novel therapeutic targets and would also allow for greater individualization of therapy and optimization of surgical outcomes.

Topics: Bariatric Surgery; Body Mass Index; Caloric Restriction; Diabetes Mellitus, Type 2; Female; Glucagon-Like Peptide 1; Glucose; Glycated Hemoglobin; Homeostasis; Humans; Incretins; Insulin Resistance; Male; Obesity, Morbid; Peptide YY; Randomized Controlled Trials as Topic; Remission Induction; Treatment Outcome; Weight Loss

Obesity continues to be a major public health problem in the United States and worldwide. While recent statistics have demonstrated that obesity rates have begun to plateau, more severe classes of obesity are accelerating at a faster pace with important implications in regards to treatment. Bariatric surgery has a profound and durable effect on weight loss, being to date one of the most successful interventions for obesity.. To provide updates to the possible role of gut hormones in post bariatric surgery weight loss and weight loss maintenance.. The current review examines the changes in gastro-intestinal hormones with bariatric surgery and the potential mechanisms by which these changes could result in decreased weight and adiposity.. The mechanism by which bariatric surgery results in body weight changes is incompletely elucidated, but it clearly goes beyond caloric restriction and malabsorption.. Changes in gastro-intestinal hormones, including increases in GLP-1, PYY, and oxyntomodulin, decreases in GIP and ghrelin, or the combined action of all these hormones might play a role in induction and long-term maintenance of weight loss.

Topics: Bariatric Surgery; Bile Acids and Salts; Caloric Restriction; Diabetes Mellitus, Type 2; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Obesity; Oxyntomodulin; Peptide YY; Postoperative Period; United States; Weight Loss

Glucagon like peptide-1 (GLP-1) is one of the gastrointestinal peptides implicated in glycaemic homeostasis. In non-obese individuals with normal glucose tolerance GLP-1 is secreted in response to nutrient intake. However, this GLP- 1 response is generally accepted to be significantly diminished in those with diabetes, obesity or both. Given that GLP-1 is secreted from enteroendocrine L cells in the intestine, it is not surprising that manipulation of the gastro- intestinal tract has been shown to alter GLP-1 secretion; particularly when this intestinal manipulation is designed to aid weight reduction. GLP-1 dynamics are altered by bariatric surgery, with an improved secretory response to nutrient intake. However, there remains debate on the mechanisms responsible for the alterations in GLP-1 dynamics. Here we review the evidence for GLP-1 dynamics after Roux-en-Y gastric bpyass (RYGB), adjustable gastric banding (AGB), biliopancreatic diversion (BPD) and sleeve gastrectomy (SG), and make comparisons between modalities. In addition, we review the potential mechanisms underlying these dynamics, other molecules that may add to the "incretin effect" and other possible roles for GLP-1 following bariatric surgery. Finally, we will offer our critique of the evidence base.

Topics: Animals; Biliopancreatic Diversion; Blood Glucose; Cross-Sectional Studies; Fasting; Female; Gastric Bypass; Gastroplasty; Glucagon-Like Peptide 1; Humans; Incretins; Longitudinal Studies; Male; Neural Pathways; Obesity, Morbid; Peptide YY; Prospective Studies; Rats; Weight Loss

Bariatric surgery managing/preventing complications of severe overweight is nowadays widely accepted as a mainstay in the treatment of morbid obesity. Its role is particularly important in type 2 diabetes developing on the base of long-standing significant overweight. The glycemic control improves within days-weeks after these surgeries, when weight loss and reduction of the visceral fat mass is barely detectable. This short term effect is probably due to an increased secretion of glucagon-like peptide and, as a consequence, an improvement in hepatic insulin sensitivity as well as the whole body glucose uptake. Besides the prolonged glucagon-like peptide effects, the favourable long term effect of these operations - lasting for 10 years even after surgery - is the decrease of visceral fat mass and elimination of harmful influence of cytokines produced by the fatty tissue. The article overviews the metabolic effects of these procedures, their undoubted advantages and potential risks.

Topics: Bariatric Surgery; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Ghrelin; Glucagon-Like Peptide 1; Humans; Hungary; Insulin; Insulin Resistance; Intra-Abdominal Fat; Male; Obesity, Morbid; Peptide YY; United States; Weight Loss

Nonalcoholic steatohepatitis (NASH) is a stage of nonalcoholic fatty liver disease (NAFLD), and in most patients, is associated with obesity and the metabolic syndrome. The current best treatment of NAFLD and NASH is weight reduction with the current options being life style modifications, with or without pharmaceuticals, and bariatric surgery. Bariatric surgery is an effective treatment option for individuals who are severely obese (body mass index ≥ 35 kg/m(2)), and provides for long-term weight loss and resolution of obesity-associated diseases in most patients. Regression and/or histologic improvement of NASH have been documented after bariatric surgery. We review the available literature reporting on the impact of the various bariatric surgery techniques on NASH.

Topics: Bariatric Surgery; Fatty Liver; Ghrelin; Glucagon-Like Peptide 1; Humans; Non-alcoholic Fatty Liver Disease; Obesity; Peptide YY; Weight Loss

Bariatric surgery is the most effective method for promoting dramatic and durable weight loss in morbidly obese subjects. Furthermore, type 2 diabetes is resolved in over 80% of patients. The mechanisms behind the amelioration in metabolic abnormalities are largely unknown but may be due to changes in energy metabolism, gut peptides and food preference. The goal of this meeting was to review the latest research to better understand the mechanisms behind the 'magic' of bariatric surgery. Replication of these effects in a non-surgical manner remains one of the ultimate challenges for the treatment of obesity and diabetes. Promising data on energy metabolism, gastrointestinal physiology, hedonic response and food intake were reviewed and discussed.

Topics: Bariatric Surgery; Energy Metabolism; Ghrelin; Glucagon-Like Peptide 1; Humans; Obesity, Morbid; Peptide YY; Weight Loss

Behavioral and pharmaceutical intervention to treat obesity and its comorbidities typically results in only a 5-10% weight loss. Thus, bariatric surgery is the most effective obesity treatment with some surgeries resulting in 30% sustained weight loss. Although this degree of weight loss has profound metabolic impact, these surgeries seem to have metabolic effects that are independent of weight loss. In support of this is the clinical literature showing rapid resolution of Type 2 diabetes mellitus (T2DM) that occurs before significant weight loss. To gain a complete understanding of the weight loss-independent effects of bariatric surgery, animal models have been developed. These are becoming more widely implemented and allow the use of pair-fed or weight-matched sham-operated controls in order to gain mechanistic insights into the mode of action of bariatric surgery. Increases in anorectic gut hormones, such as glucagon-like peptide-1 and peptide YY, or decreases in the orexigenic hormone ghrelin have been seen and are implicated as mediators of weight loss-independent actions of bariatric surgery. Changes in nutrient processing and sensing may also have a mechanistic role that is independent of, or that regulates, gut hormone responses to these surgeries. Ultimately, the hope is that understanding the mechanisms of bariatric surgeries will aid in the development of less invasive surgeries or pharmacological therapies that are more specifically, and perhaps individually, targeted at weight loss and/or resolution of T2DM.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Type 2; Gastric Bypass; Gastrointestinal Hormones; Glucagon-Like Peptide 1; Humans; Malabsorption Syndromes; Peptide YY; Weight Loss

The clinical outcomes achieved by bariatric surgery have been impressive. However, the physiologic mechanisms and complex metabolic effects of bariatric surgery are only now beginning to be understood. Ongoing research has contributed a large amount of data and shed new light on the science behind obesity and its treatment, and this article reviews the current understanding of metabolic and bariatric surgery physiology.

Topics: Bariatric Surgery; Diabetes Mellitus, Type 2; Gastric Bypass; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon-Like Peptide 1; Humans; Leptin; Neuropeptide Y; Obesity, Morbid; Peptide YY; Weight Loss

Bariatric surgery is the most effective treatment modality for obesity, resulting in durable weight loss and amelioration of obesity-associated comorbidities, particularly type 2 diabetes mellitus (T2DM). Moreover, the metabolic benefits of bariatric surgery occur independently of weight loss. There is increasing evidence that surgically induced alterations in circulating gut hormones mediate these beneficial effects of bariatric surgery. Here, we summarise current knowledge on the effects of different bariatric procedures on circulating gut hormone levels. We also discuss the theories that have been put forward to explain the weight loss and T2DM resolution following bariatric surgery. Understanding the mechanisms mediating these beneficial outcomes of bariatric surgery could result in new non-surgical treatment strategies for obesity and T2DM.

Topics: Bariatric Surgery; Caloric Restriction; Diabetes Mellitus, Type 2; Energy Metabolism; Ghrelin; Glucagon-Like Peptide 1; Humans; Obesity; Peptide YY; Weight Loss

Roux-en-Y gastric bypass is a well-accepted tool for the treatment of obesity and, compared to conventional weight loss methods (eg, diet and exercise) and other weight loss surgeries (eg, gastric banding), it results in considerable weight loss that is maintained long term. Although successful, the mechanisms for weight loss are not completely understood and it is thought that gastrointestinal hormones play a role. Several gastrointestinal hormones have been identified for their effects on appetite, including glucagon-like peptide-1 (GLP-1), peptide tyrosine-tyrosine (PYY), leptin, and ghrelin. This review encompasses a literature search that included 45 primary articles and shows that there are alterations in GLP-1, PYY, leptin, and ghrelin postoperatively. GLP-1 and PYY concentrations were usually found to be higher, whereas ghrelin levels were typically lower post- Roux-en-Y gastric bypass than in individuals with obesity, those who were overweight or of normal weight, and in those who underwent procedures other than Roux-en-Y gastric bypass or who achieved weight loss by lifestyle modification. An understanding of how gastrointestinal hormones change after Roux-en-Y gastric bypass may help dietetics practitioners optimize nutrition care for this patient population. A review of the literature also highlighted some research gaps that should be taken into consideration when designing future studies.

Topics: Appetite Regulation; Follow-Up Studies; Gastric Bypass; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Leptin; Obesity, Morbid; Peptide YY; Treatment Outcome; Weight Loss

Gastric bypass surgery (GBP), in addition to weight loss, results in dramatic remission of type 2 diabetes (T2DM). The mechanisms by which this remission occurs are unclear. Besides weight loss and caloric restriction, the changes in gut hormones that occur after GBP are increasingly gaining recognition as key players in glucose control. Incretins are gut peptides that stimulate insulin secretion postprandially; the levels of these hormones, particularly glucagon-like peptide-1, increase after GBP in response to nutrient stimulation. Whether these changes are causal to changes in glucose homeostasis remain to be determined. The purpose of this review is to assess the evidence on incretin changes and T2DM remission after GBP, and the possible mechanisms by which these changes occur. Our goals are to provide a thorough update on this field of research so that recommendations for future research and criteria for bariatric surgery can be evaluated.

Topics: Animals; Diabetes Mellitus, Type 2; Evidence-Based Medicine; Gastric Bypass; Gastric Emptying; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon-Like Peptide 1; Gluconeogenesis; Glucose; Homeostasis; Humans; Incretins; Intestine, Small; Leptin; Liver; Obesity, Morbid; Peptide YY; Randomized Controlled Trials as Topic; Remission Induction; Weight Loss

Bariatric surgery is the only effective treatment for morbid obesity in the long term. Gut hormones are key players in the metabolic mechanisms causing obesity. Furthermore gut hormones are involved in the signalling process of hunger and satiety which leads to the control of nutrient intake. In this review, the role of these hormones as facilitators of appetite control after bariatric and metabolic surgery will be explored.

Topics: Animals; Appetite Regulation; Bariatric Surgery; Cholecystokinin; Eating; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Hunger; Obesity, Morbid; Peptide YY; Satiation; Satiety Response; Weight Loss

The literature presented in this paper argues that our limited ability to maintain energy balance in a weight-reduced state is the product of our difficulty in compensating for the weight loss-induced reduction in total energy expenditure. The end result, translated into the overwhelming complexity of preserving long-term weight loss, is presented as being a consequence of compromised appetite control. Given the present-day food landscape and the resultant susceptibility to passive overconsumption, the focus of this review will be on the peripheral ("bottom-up") signals (leptin, PYY, ghrelin, and GLP-1) and the evidence highlighting their influence on feeding behaviour. As we continue studying paradigms of body mass reduction, specifically the data emerging from patients of bariatric surgery, it is becoming clearer that counter-regulatory adaptations, possibly through down-(leptin, PYY, and GLP-1) or upregulation (ghrelin) of peptides, have an impact on energy balance. In itself, food deprivation influences some of the peptides that ultimately provide the physiological input for the overt expression of feeding behaviour; these peripheral adaptations are expected to serve as feeding cues--cues that, in the end, can serve to compromise the maintenance of energy balance. In a potentially novel intervention to increase compliance to long-term reductions in energy intake, it is proposed that manipulating the pattern of food intake to favourably alter the profile of gastrointestinal peptides would lead to better dietary control.

Topics: Appetite; Appetite Regulation; Energy Metabolism; Food; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Leptin; Peptide Hormones; Peptide YY; Time Factors; Weight Loss

Obesity is a rapidly increasing, worldwide epidemic. Despite recent scientific advances, no currently recommended dietary program or medication results in long-term weight loss of more than 10% of body weight for the vast majority of people who attempt these interventions. Hence, surgical intervention is recommended for patients with a BMI > or =40 kg/m2. Although surgery is an effective, sustainable treatment of obesity, it can be associated with potentially significant perioperative risks and long-term complications. Current research is focused on developing a medical therapy, which produces more effective and sustainable weight loss, yet avoids the risks inherent in major surgery. With a reduced risk profile, such therapy could also be appropriately offered to those who are less obese and, in theory, help those who have BMIs as low as 27 kg/m2. Toward that end, numerous scientists are working to both unravel the pathophysiology of obesity and to determine why surgical intervention is so effective. This review briefly examines the current status of obesity pathophysiology and management, the reasons for failure of conventional medical treatments, and the success of surgical intervention. Finally, future areas of research are discussed.

Topics: Animals; Arcuate Nucleus of Hypothalamus; Bariatric Surgery; Gastric Bypass; Ghrelin; Humans; Hypothalamus; Obesity; Obesity, Morbid; Peptide Fragments; Peptide YY; Satiety Response; Signal Transduction; Weight Loss

This article aims to critically review the literature, describing the possible implications of different bariatric surgery techniques in gastrointestinal peptides and their relation with the neural paths involved in the central regulation of appetite and satiety: the gut-brain axis.. Bariatric surgery operations change orexigenic and anorexigenic gastrointestinal peptide levels. Forty-one studies were analyzed in order to understand the effects of different operations on the behavior of gut peptides (ghrelin, cholecystokinin, peptide YY, glucagon-like peptide-1, gastric inhibitory polypeptide, pancreatic polypeptide). The authors have tried to correlate these findings with weight loss/maintenance via different surgical techniques.. The present line of research is recent and there is a lack of comparability between studies. There are different design approaches and study protocols, different laboratorial exams. Prospective long-term studies with larger samples are needed to clarify the effects of bariatric operations on the gut-brain axis.

Topics: Appetite Regulation; Bariatric Surgery; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Obesity, Morbid; Pancreatic Polypeptide; Peptide Hormones; Peptide YY; Satiety Response; Weight Loss

Recent advances in obesity research focused on neuroendocrine control of food intake, appetite and body weight balance. Gut hormones, which are sequentially released from different regions of the gut, send signals to the areas of appetite control in the central nervous system causing a release of counter-regulatory hormones also originating from the gastrointestinal system. Ghrelin, a peptide secreted from the gastric fundus is released just before meal intake and stimulates hunger and food intake. Recently, peptide YY has been suggested to counteract ghrelin by inducing satiety and reducing appetite and caloric intake. While the effects of PYY on various gastrointestinal functions are well described, its action on weight loss is less known. Controversial results on the effect of exogenous administration of PYY(3-36) opened the discussion on the respective roles of PYY and/or PYY(3-36) in body weight homeostasis in man.

Topics: Appetite Regulation; Brain; Humans; Obesity; Peptide YY; Weight Loss

The gut-derived peptide hormones glucagon-like peptide-1 (GLP-1), oxyntomodulin (OXM), and peptide YY (PYY) are regulators of energy intake and glucose homeostasis and are thought to contribute to the glucose-lowering effects of bariatric surgery.. To establish the metabolomic effects of a combined infusion of GLP-1, OXM, and PYY (tripeptide GOP) in comparison to a placebo infusion, Roux-en-Y gastric bypass (RYGB) surgery, and a very low-calorie diet (VLCD).. Subanalysis of a single-blind, randomized, placebo-controlled study of GOP infusion (ClinicalTrials.gov NCT01945840), including VLCD and RYGB comparator groups.. Twenty-five obese patients with type 2 diabetes or prediabetes were randomly allocated to receive a 4-week subcutaneous infusion of GOP (n = 14) or 0.9% saline control (n = 11). An additional 22 patients followed a VLCD, and 21 underwent RYGB surgery.. Plasma and urine samples collected at baseline and 4 weeks into each intervention were subjected to cross-platform metabolomic analysis, followed by unsupervised and supervised modeling approaches to identify similarities and differences between the effects of each intervention.. Aside from glucose, very few metabolites were affected by GOP, contrasting with major metabolomic changes seen with VLCD and RYGB.. Treatment with GOP provides a powerful glucose-lowering effect but does not replicate the broader metabolomic changes seen with VLCD and RYGB. The contribution of these metabolomic changes to the clinical benefits of RYGB remains to be elucidated.

Topics: Adult; Aged; Blood Glucose; Caloric Restriction; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Gastric Bypass; Gastrointestinal Hormones; Glucagon-Like Peptide 1; Humans; Infusions, Subcutaneous; Male; Metabolomics; Middle Aged; Obesity, Morbid; Oxyntomodulin; Peptide YY; Single-Blind Method; Treatment Outcome; Weight Loss; Young Adult

To assess the impact of the sodium-glucose co-transporter-2 (SGLT2) inhibitor empagliflozin (25 mg once-daily), dietary energy restriction, or both combined, on circulating appetite-regulatory peptides in people with type 2 diabetes (T2D) and overweight or obesity.. The mean weight loss in each group at 24 weeks was 0.44, 1.91, 2.22 and 5.74 kg, respectively. The change from baseline to 24 weeks in postprandial total PYY was similar between experimental groups and placebo only (mean difference [95% CI]: -8.6 [-28.6 to 11.4], 13.4 [-6.1 to 33.0] and 1.0 [-18.0 to 19.9] pg/ml in placebo-plus diet, empagliflozin-only and empagliflozin-plus-diet groups, respectively [all P ≥ .18]). Similarly, there was no consistent pattern of difference between groups for postprandial total GLP-1, acylated ghrelin and subjective appetite perceptions.. In people with T2D and overweight or obesity, changes in postprandial appetite-regulatory gut peptides may not underpin the less than predicted weight loss observed with empagliflozin therapy.. NCT02798744, www.. gov; 2015-001594-40, www.EudraCT.ema.europa.eu; ISRCTN82062639, www.ISRCTN.org.

Topics: Adult; Aged; Appetite; Benzhydryl Compounds; Diabetes Mellitus, Type 2; Double-Blind Method; Ghrelin; Glucagon-Like Peptide 1; Glucose; Glucosides; Humans; Hypoglycemic Agents; Middle Aged; Obesity; Overweight; Peptide YY; Sodium-Glucose Transporter 2 Inhibitors; Weight Loss

Exercise-induced weight loss can occur for several reasons, including changes in circulatory levels of appetite-regulating hormones. The purpose of this study was to compare the effect of various training programs on fasting serum levels of acylated ghrelin, peptide YY 3-36 (PYY

Topics: Appetite; Body Composition; Body Mass Index; Body Weight; Ghrelin; Glucagon-Like Peptide 1; Humans; Male; Overweight; Peptide Fragments; Peptide YY; Physical Conditioning, Human; Sedentary Behavior; Weight Loss

Diet-induced weight loss (WL) is usually accompanied by increased appetite, a response that seems to be absent when ketogenic diets are used. It remains unknown if sex modulates the appetite suppressant effect of ketosis.. The aim of this study was to examine if sex modulates the impact of WL-induced changes in appetite and if ketosis alters these responses.. Ninety-five individuals (55 females) with obesity (BMI [kg/m 2]: 37  ± 4) underwent 8 wk of a very-low-energy diet, followed by 4 wk of refeeding and weight stabilization. Body composition, plasma concentration of β-hydroxybutyrate (β-HB) and appetite-related hormones (active ghrelin, active glucagon-like peptide 1 [GLP-1], total peptide YY [PYY], cholecystokinin and insulin), and subjective feelings of appetite were measured at baseline, week 9 in ketosis, and week 13 out of ketosis.. The mean WL at week 9 was 17% for males and 15% for females, which was maintained at week 13. Weight, fat, and fat-free mass loss were greater in males (P < 0.001 for all) and the increase in β-HB at week 9 higher in females (1.174 ± 0.096 compared with 0.783 ± 0.112 mmol/L, P = 0.029). Basal and postprandial GLP-1 and postprandial PYY (all P < 0.05) were significantly different for males and females. There were no significant sex × time interactions for any other appetite-related hormones or subjective feelings of appetite. At week 9, basal GLP-1 was decreased only in males (P < 0.001), whereas postprandial GLP-1 was increased only in females (P < 0.001). No significant changes in postprandial PYY were observed over time for either sex.. Ketosis appears to have a greater beneficial impact on GLP-1 in females. However, sex does not seem to modulate the changes in the secretion of other appetite-related hormones, or subjective feelings of appetite, seen with WL, regardless of the ketotic state. This trial was registered at clinicaltrials.gov as NCT01834859.

Topics: Adolescent; Adult; Aged; Appetite; Cholecystokinin; Female; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin; Ketosis; Male; Middle Aged; Obesity; Peptide YY; Sex Factors; Weight Loss; Young Adult

Roux-en-Y gastric bypass (RYGB) augments postprandial secretion of glucagon-like peptide 1 (GLP-1), oxyntomodulin (OXM), and peptide YY (PYY). Subcutaneous infusion of these hormones ("GOP"), mimicking postprandial levels, reduces energy intake. Our objective was to study the effects of GOP on glycemia and body weight when given for 4 weeks to patients with diabetes and obesity.. In this single-blinded mechanistic study, obese patients with prediabetes/diabetes were randomized to GOP (. GOP infusion improves glycemia and reduces body weight. It achieves superior glucose tolerance and reduced glucose variability compared with RYGB and VLCD. GOP is a viable alternative for the treatment of diabetes with favorable effects on body weight.

Topics: Adult; Blood Glucose; Blood Glucose Self-Monitoring; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glucagon-Like Peptide 1; Humans; Hypoglycemia; Infusions, Subcutaneous; Insulin; Male; Meals; Middle Aged; Obesity; Oxyntomodulin; Peptide YY; Postprandial Period; Prediabetic State; Single-Blind Method; Weight Loss

Strong compensatory responses, with reduced resting metabolic rate (RMR), increased exercise efficiency (ExEff) and appetite, are activated when weight loss (WL) is achieved with continuous energy restriction (CER), which try to restore energy balance. Intermittent energy restriction (IER), where short spells of energy restriction are interspaced by periods of habitual energy intake, may offer some protection in minimizing those responses. We aimed to compare the effect of IER versus CER on body composition and the compensatory responses induced by WL.. Changes in body weight (≈12.5% WL) and composition were similar in both groups. Fasting RQ and ExEff at 10 W increased in both groups. Losing weight, either by IER or CER dieting, did not induce significant changes in subjective appetite ratings. RMR decreased and ExEff at 25 and 50 W increased (P < 0.001 for all) in IER group only. Basal and postprandial AG increased (P < 0.05) in IER group, whereas basal active GLP-1 decreased (P = 0.033) in CER group only. Postprandial CCK decreased in both groups (P = 0.0012 and P = 0.009 for IER and CER groups, respectively). No between group differences were apparent for any of the outcomes.. The technique used to achieve energy restriction, whether it is continuous or intermittent, does not appear to modulate the compensatory mechanisms activated by weight loss.. NCT02169778 (the study was registered in clinicaltrial.gov).

Topics: Adult; Basal Metabolism; Body Composition; Body Weight; Caloric Restriction; Cholecystokinin; Diet, Reducing; Eating; Energy Intake; Exercise; Ghrelin; Glucagon-Like Peptide 1; Humans; Hunger; Middle Aged; Norway; Obesity; Oxygen Consumption; Peptide YY; Weight Loss

Although different hypotheses have been proposed, the underlying mechanism(s) of the weight loss induced by laparoscopic sleeve gastrectomy (LSG) is still unknown. The aim of this study was to determine whether eating the same meal at different rates (fast vs. slow feeding) evokes different post-prandial anorexigenic gut peptide responses in ten obese patients undergoing LSG. Circulating levels of GLP-1, PYY, glucose, insulin and triglycerides were measured before and 3 months after LSG. Visual analogue scales were used to evaluate the subjective feelings of hunger and satiety. Irrespective of the operative state, either fast or slow feeding did not stimulate GLP-1 release (vs. 0 min); plasma levels of PYY were increased (vs. 0 min) by fast and slow feeding only after LSG. There were no differences in post-prandial levels of GLP-1 when comparing fast to slow feeding or pre-to-post-operative state. Plasma levels of PYY after fast or slow feeding were higher in post, rather than pre-operative state, with no differences when comparing PYY release after fast and slow feeding. Hunger and satiety were decreased and increased, respectively, (vs. 0 min) by food intake. Fast feeding evoked a higher satiety than slow feeding in both pre- and post-operative states, with no differences in hunger. In both pre- and post-operative states, there were similar responses for hunger and satiety after food intake. Finally, LSG improved insulin resistance after either fast or slow feeding. These (negative) findings would suggest a negligible contribution of the anorexigenic gut peptide responses in LSG-induced weight loss.

Topics: Adult; Appetite Regulation; Body Mass Index; Combined Modality Therapy; Diet, Reducing; Enteroendocrine Cells; Feeding Behavior; Female; Gastrectomy; Gastroplasty; Glucagon-Like Peptide 1; Humans; Insulin Resistance; Italy; Laparoscopy; Male; Middle Aged; Obesity, Morbid; Peptide YY; Postprandial Period; Time Factors; Weight Loss

The relationship between dietary macronutrient composition and appetite is controversial. We examined the effects of a year-long low-carbohydrate diet compared to a low-fat diet on appetite-related hormones and self-reported change in appetite.. A total of 148 adults with a body mass index 30-45 kg/m(2), who were free of diabetes, cardiovascular disease and chronic kidney disease at baseline were randomly assigned to either a low-carbohydrate diet (carbohydrate [excluding dietary fiber]<40 g/day; N = 75) or a low-fat diet (<30% energy from fat, <7% from saturated fat; N = 73). Participants in both groups attended individual and group dietary counseling sessions where they were provided the same behavioral curriculum and advised to maintain baseline levels of physical activity. Appetite and appetite-related hormones were measured at 0, 3, 6 and 12 months of intervention. At 12 months, mean changes (95% CI) in peptide YY were -34.8 pg/mL (-41.0 to -28.6) and in the low-carbohydrate group and -44.2 pg/mL (-50.4 to -38.0) in the low-fat group (net change: 9.54 pg/mL [0.6 to 18.2]; p = 0.036). Approximately 99% of dietary effects on peptide YY are explained by differences in dietary macronutrient content. There was no difference in change in ghrelin or self-reported change in appetite between the groups.. A low-fat diet reduced peptide YY more than a low-carbohydrate diet. These findings suggest that satiety may be better preserved on a low-carbohydrate diet, as compared to a low fat diet.. clinicaltrials.gov Identifier: NCT00609271.

Topics: Adult; Aged; Appetite Regulation; Biomarkers; Counseling; Diet, Carbohydrate-Restricted; Diet, Fat-Restricted; Exercise; Female; Ghrelin; Humans; Male; Middle Aged; New Orleans; Obesity; Peptide YY; Satiation; Time Factors; Treatment Outcome; Weight Loss; Young Adult

Exaggerated postprandial secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) may explain appetite reduction and weight loss after Roux-en-Y gastric bypass (RYGB), but causality has not been established. We hypothesized that food intake decreases after surgery through combined actions from GLP-1 and PYY. GLP-1 actions can be blocked using the GLP-1 receptor antagonist Exendin 9-39 (Ex-9), whereas PYY actions can be inhibited by the administration of a dipeptidyl peptidase-4 (DPP-4) inhibitor preventing the formation of PYY. In study 1, food intake decreased by 35% following RYGB compared with before surgery. Before surgery, GLP-1 receptor blockage increased food intake but no effect was seen postoperatively, whereas PYY secretion was markedly increased. In study 2, combined GLP-1 receptor blockage and DPP-4 inhibitor mediated lowering of PYY. Blockade of actions from only one of the two L-cell hormones, GLP-1 and PYY

Topics: Appetite; Appetite Regulation; Cross-Over Studies; Denmark; Diabetes Mellitus, Type 2; Eating; Female; Gastric Bypass; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Male; Obesity, Morbid; Peptide Fragments; Peptide YY; Treatment Outcome; Weight Loss

It is unknown whether leptin and peptide YY (PYY) influence changes in resting energy expenditure (REE), independently of fat mass (FM) and fat-free mass (FFM) in addition to changes in other energy expenditure (EE) components during weight loss.. The objective of the study was to examine the relationships between leptin, PYY, and body composition with different EE components before and after weight loss and whether changes in leptin and PYY were associated with differences in predicted vs measured REE after the intervention.. This was a randomized controlled design.. The study was conducted in a laboratory.. Participants were ninety-three overweight/obese postmenopausal women (aged 58.1 ± 4.8 y; body mass index 32.1 ± 4.3 kg/m(2)).. Interventions included a 6-month caloric restriction diet alone or caloric restriction diet+resistance training.. Body composition (dual energy x-ray absorptiometry), REE (indirect calorimetry), total EE (TEE; doubly labeled water), and fasting leptin and total PYY before and after weight loss were measured.. Both interventions yielded significant decreases in weight, FFM, REE, and leptin, whereas a significant time × group interaction was noted for FM (greater decrease in FM in the diet+resistance training group) (P < .05 for all outcomes). No significant differences in TEE, physical activity EE, and PYY were noted between baseline and after the intervention. Age, FFM, leptin, and PYY were the best predictors of baseline REE (R(2) = 0.77; P = .0001), whereas age, FFM, and FM were associated with REE after the intervention (R(2) = 0.88; P = .0001). The same predictors, except for leptin, were significantly related to TEE at baseline (R(2) = 0.70; P = .0001) and after the intervention (R(2) = 0.29; P = .0001), whereas only PYY was a significant predictor of physical activity EE at baseline and after the intervention. Changes in FM and leptin accounted for 27% of the variance in ΔREE (P = .0001). Greater predicted vs measured REE was noted after the intervention (P = .02). However, Δ leptin and ΔPYY were not significant predictors of the differences between postintervention measurement and predicted REE.. Δ Leptin and ΔFM were strong contributors to changes in REE. However, Δ leptin and ΔPYY were not significant predictors of the differences between predicted and measured REE after the intervention.

Topics: Basal Metabolism; Caloric Restriction; Diet, Reducing; Down-Regulation; Energy Metabolism; Female; Humans; Leptin; Middle Aged; Obesity; Overweight; Peptide YY; Rest; Weight Loss

Gut hormones change with weight loss in adults but are not well studied in obese youth.. The primary aim was to evaluate how gut hormones and subjective appetite measure change with dietary weight loss in obese adolescents.. Participants were a subset of those taking part in the 'Eat Smart Study'. They were aged 10-17 years with body mass index (BMI) > 90th centile and were randomized to one of three groups: wait-listed control, structured reduced carbohydrate or structured low-fat dietary intervention for 12 weeks. Outcomes were fasting glucose, insulin, leptin, adiponectin, total amylin, acylated ghrelin, active glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide (GIP), pancreatic polypeptide (PP) and total peptide tyrosine-tyrosine. Pre- and postprandial subjective sensations of appetite were assessed using visual analogue scales.. Of 87 'Eat Smart' participants, 74 participated in this sub-study. The mean (standard deviation) BMI z-score was 2.1 (0.4) in the intervention groups at week 12 compared with 2.2 (0.4) in the control group. Fasting insulin (P = 0.05) and leptin (P = 0.03) levels decreased, while adiponectin levels increased (P = 0.05) in the intervention groups compared with control. The intervention groups were not significantly different from each other. A decrease in BMI z-score at week 12 was associated with decreased fasting insulin (P < 0.001), homeostatic model of assessment-insulin resistance (P < 0.001), leptin (P < 0.001), total amylin (P = 0.03), GIP (P = 0.01), PP (P = 0.02) and increased adiponectin (P < 0.001). There was no significant difference in appetite sensations.. Modest weight loss in obese adolescents leads to changes in some adipokines and gut hormones that may favour weight regain.

Topics: Adiponectin; Adolescent; Adult; Appetite; Body Mass Index; Body Weight; Fasting; Female; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Leptin; Male; Pediatric Obesity; Peptide YY; Postprandial Period; Weight Loss

Energetic adaptations induced by bariatric surgery have not been studied in adolescents or for extended periods postsurgery. Energetic, metabolic, and neuroendocrine responses to Roux-en-Y gastric bypass (RYGB) surgery were investigated in extremely obese adolescents.. At baseline and at 1.5, 6, and 12 months post-baseline, 24-h room calorimetry, body composition, and fasting blood biochemistries were measured in 11 obese adolescents relative to five matched controls.. In the RYGB group, mean weight loss was 44 ± 19 kg at 12 months. Total energy expenditure (TEE), activity EE, basal metabolic rate (BMR), sleep EE, and walking EE significantly declined by 1.5 months (P = 0.001) and remained suppressed at 6 and 12 months. Adjusted for age, sex, fat-free mass, and fat mass, EE was still lower than baseline (P = 0.001). Decreases in serum insulin, leptin, and triiodothyronine (T3), gut hormones, and urinary norepinephrine (NE) paralleled the decline in EE. Adjusted changes in TEE, BMR, and/or sleep EE were associated with decreases in insulin, homeostatic model assessment, leptin, thyroid stimulating hormone, total T3, peptide YY3-36, glucagon-like peptide-2, and urinary NE and epinephrine (P = 0.001-0.05).. Energetic adaptations in response to RYGB-induced weight loss are associated with changes in insulin, adipokines, thyroid hormones, gut hormones, and sympathetic nervous system activity and persists 12 months postsurgery.

Topics: Adaptation, Physiological; Adipokines; Adolescent; Bariatric Surgery; Basal Metabolism; Body Composition; Energy Metabolism; Female; Gastrointestinal Hormones; Humans; Insulin; Leptin; Male; Obesity, Morbid; Pediatric Obesity; Peptide Fragments; Peptide YY; Weight Loss

High-protein diets are an effective means for weight loss (WL), but the mechanisms are unclear. One hypothesis relates to the release of gut hormones by either protein or amino acids (AA). The present study involved overweight and obese male volunteers (n 18, mean BMI 36·8 kg/m2) who consumed a maintenance diet for 7 d followed by fully randomised 10 d treatments with three iso-energetic WL diets, i.e. with either normal protein (NP, 15% of energy) or high protein (HP, 30%) or with a combination of protein and free AA, each 15% of energy (NPAA). Psychometric ratings of appetite were recorded hourly. On day 10, plasma samples were taken at 30 min intervals over two consecutive 5 h periods (covering post-breakfast and post-lunch) and analysed for AA, glucose and hormones (insulin, total glucose-dependent insulinotropic peptide, active ghrelin and total peptide YY (PYY)) plus leucine kinetics (first 5 h only). Composite hunger was 16% lower for the HP diet than for the NP diet (P<0·01) in the 5 h period after both meals. Plasma essential AA concentrations were greatest within 60 min of each meal for the NPAA diet, but remained elevated for 3-5 h after the HP diet. The three WL diets showed no difference for either fasting concentrations or the postprandial net incremental AUC (net AUCi) for insulin, ghrelin or PYY. No strong correlations were observed between composite hunger scores and net AUCi for either AA or gut peptides. Regulation of hunger may involve subtle interactions, and a range of signals may need to be integrated to produce the overall response.

Topics: Adult; Aged; Amino Acids; Appetite; Area Under Curve; Blood Glucose; Body Composition; Body Mass Index; Body Weight; Diet, Reducing; Dietary Proteins; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Ghrelin; Humans; Hunger; Intestinal Mucosa; Male; Middle Aged; Obesity; Peptide YY; Postprandial Period; Psychometrics; Tryptophan; Weight Loss; Young Adult

Inhibition of diacylglycerol acyltransferase 1 (DGAT1) is a potential treatment modality for patients with type 2 diabetes mellitus and obesity, based on preclinical data suggesting it is associated with insulin sensitization and weight loss. This randomized, placebo-controlled, phase 1 study in 62 overweight or obese men explored the effects and tolerability of AZD7687, a reversible and selective DGAT1 inhibitor.. Multiple doses of AZD7687 (1, 2.5, 5, 10 and 20 mg/day, n = 6 or n = 12 for each) or placebo (n = 20) were administered for 1 week. Postprandial serum triacylglycerol (TAG) was measured for 8 h after a standardized 45% fat meal. Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) were measured and a paracetamol challenge was performed to assess gastric emptying.. Dose-dependent reductions in postprandial serum TAG were demonstrated with AZD7687 doses ≥5 mg compared with placebo (p < 0.01). Significant (p < 0.001) increases in plasma GLP-1 and PYY levels were seen at these doses, but no clear effect on gastric emptying was demonstrated at the end of treatment. With AZD7687 doses >5 mg/day, gastrointestinal (GI) side effects increased; 11/18 of these participants discontinued treatment owing to diarrhoea.. Altered lipid handling and hormone secretion in the gut were demonstrated during 1-week treatment with the DGAT1 inhibitor AZD7687. However, the apparent lack of therapeutic window owing to GI side effects of AZD7687, particularly diarrhoea, makes the utility of DGAT1 inhibition as a novel treatment for diabetes and obesity questionable.

Topics: Acetates; Adult; Anti-Obesity Agents; Diabetes Mellitus, Type 2; Diacylglycerol O-Acyltransferase; Diarrhea; Dose-Response Relationship, Drug; Gastric Emptying; Glucagon-Like Peptide 1; Humans; Intestinal Absorption; Male; Middle Aged; Obesity; Peptide YY; Pyrazines; Treatment Outcome; Weight Loss

There is limited evidence with regard to the effect of different sources of protein on appetite during weight loss. Vegetarian and meat-based high-protein diets may have contrasting effects on appetite and biomarkers of protein-induced satiety.. The aim was to assess appetite response to meat or vegetarian high-protein weight-loss (HPWL) diets in obese men to monitor plasma amino acid profile and gut peptide response as potential satiety biomarkers.. Twenty obese [body mass index (in kg/m²): 34.8] men participated in a dietary intervention study. After 3 d of a maintenance diet, they were provided in a crossover design with either a vegetarian HPWL (Soy-HPWL) or a meat-based HPWL (Meat-HPWL) diet for 2 wk. Both diets comprised 30% protein, 30% fat, and 40% carbohydrate, provided to measured resting metabolic rate. Body weight and the motivation to eat were measured daily. Plasma satiety biomarkers were collected during a test-meal challenge (5 h) at the end of each diet period.. Over the 2 wk, subjects lost, on average, 2.41 and 2.27 kg with consumption of the Soy- and Meat-HPWL diets, respectively [P = 0.352; SE of the difference (SED): 0.1]. ANOVA confirmed that subjectively rated hunger (P = 0.569; SED: 3.8), fullness (P = 0.404; SED: 4.1), desire to eat (P = 0.356; SED: 3.7), preservation of lean body mass (P = 0.334; SED: 0.2), and loss of percentage fat mass (P = 0.179; SED: 0.2) did not differ between the 2 HPWL diets. There were differences in absolute concentrations of ghrelin and peptide YY between the 2 HPWL diets, although the response as net area under the curve was not different.. Appetite control and weight loss were similar for both HPWL diets. Gut hormone profile was similar between the diets, which suggests that vegetarian diets can be as effective as meat-based diets for appetite control during weight loss.

Topics: Adult; Aged; Amino Acids; Appetite Regulation; Biomarkers; Body Mass Index; Cross-Over Studies; Diet, Reducing; Diet, Vegetarian; Dietary Proteins; Food Preferences; Ghrelin; Humans; Male; Meat; Middle Aged; Obesity; Peptide YY; Plant Proteins, Dietary; Satiety Response; Scotland; Soybean Proteins; Weight Loss

A diet rich in dairy and calcium (Ca) has been variably associated with improvements in body composition and decreased risk of type 2 diabetes. Our objective was to determine if a dietary pattern high in dairy and Ca improves weight loss and subjective appetite to a greater extent than a low dairy/Ca diet during energy restriction in overweight and obese adults with metabolic syndrome.. A total of 49 participants were randomized to one of two treatment groups: Control (low dairy, ≈ 700 mg/day Ca, -500 kcal/day) or Dairy/Ca (high dairy, ≈ 1400 mg/day Ca, -500 kcal/day) for 12 weeks. Body composition, subjective ratings of appetite, food intake, plasma satiety hormones, glycemic response and inflammatory cytokines were measured.. Control (-2.2 ± 0.5 kg) and Dairy/Ca (-3.3 ± 0.6 kg) had similar weight loss. Based on self-reported energy intake, the percentage of expected weight loss achieved was higher with Dairy/Ca (82.1 ± 19.4%) than Control (32.2 ± 7.7%; P=0.03). Subjects in the Dairy/Ca group reported feeling more satisfied (P=0.01) and had lower dietary fat intake (P=0.02) over 12 weeks compared with Control. Compared with Control, Dairy/Ca had higher plasma levels of peptide tyrosine tyrosine (PYY, P=0.01) during the meal tolerance test at week 12. Monocyte chemoattractant protein-1 was reduced at 30 min with Dairy/Ca compared with Control (P=0.04).. In conclusion, a dairy- and Ca-rich diet was not associated with greater weight loss than control. Modest increases in plasma PYY concentrations with increased dairy/Ca intake, however, may contribute to enhanced sensations of satisfaction and reduced dietary fat intake during energy restriction.

Topics: Adult; Appetite; Area Under Curve; Blood Glucose; Body Composition; Calcium, Dietary; Chemokine CCL2; Dairy Products; Diet, Reducing; Energy Intake; Female; Homeostasis; Humans; Insulin; Linear Models; Male; Middle Aged; Motor Activity; Obesity; Overweight; Peptide YY; Risk Factors; Weight Loss; Young Adult

Reduced postprandial secretion of peptide YY (PYY), glucagon-like peptide-1 (GLP-1), cholecystokinin, and increased hunger was reported after a single dose of orlistat, an inhibitor of intestinal lipase. As yet, the influence of long-term therapy with orlistat on PYYand GLP-1 release has not been studied. Our study was aimed at assessing the influence of 8-week therapy with orlistat as a component of a weight loss program on pre-prandial circulating PYY and GLP-1 levels.. Forty obese women, without concomitant diseases, were randomly allocated to groups receiving orlistat or placebo during an 8-week weight management program. Body mass, body composition and plasma levels of PYY, GLP-1 and insulin (for QUICKI calculation) were determined prior to and at the end of therapy.. Women treated with orlistat obtained significantly greater body and fat mass loss than those receiving placebo (9.0 ± 3.1 vs. 5.9 ± 3.2% and 21.9 ± 10.9 vs. 7.4 ± 15.6%, respectively). Only in those treated with orlistat a slight, but significant increase of the QUICKI was found (8.0 ± 16.5 vs. -0.1 ± 12.7 %, respectively). Weight loss was followed by a significant increase of plasma levels of PYY and GLP-1 in group treated with orlistat, and was about 2-times greater than receiving placebo. The increase was independent of body mass changes.. The long-term inhibition of intestinal lipase by orlistat increases the pre-prandial levels of GLP-1 and PYY, independent of body mass changes. Therefore, it seems that long-term treatment with orlistat may exert hunger suppressing and insulin sensitizing incretin effect beyond weight reduction.

Topics: Body Mass Index; Body Weight; Double-Blind Method; Female; Glucagon-Like Peptide 1; Humans; Insulin; Intestinal Mucosa; Intestines; Lactones; Lipase; Obesity; Orlistat; Peptide YY; Weight Loss

Weight loss induced by endurance exercise is often disappointing, possibly due to an increase in energy intake mediated through greater appetite. The aim of this study was to evaluate fasting, postprandial, and postexercise appetite regulation after an intervention prescribing two amounts of endurance exercise. Sixty-four sedentary, overweight, healthy young men were randomized to control (CON), moderate-dose (MOD: ≈ 30 min/day), or high-dose (HIGH: ≈ 60 min/day) endurance exercise for 12 wk. Along with subjective appetite ratings, plasma ghrelin, glucagon, insulin, peptide YY3-36, glucose, free fatty acids, and glycerol were measured during fasting and in relation to a breakfast meal and an acute bout of exercise, both at baseline and at follow-up. Ad libitum lunch energy intake was evaluated 3 h after the breakfast meal. Despite different amounts of endurance exercise, the subjects lost similar amounts of fat mass (MOD: 4.2 ± 0.5 kg; HIGH: 3.7 ± 0.5 kg). Fasting and postprandial insulin decreased ≈ 20% in both exercise groups (P < 0.03 vs. CON). Appetite measurements were not upregulated in the fasting and postprandial states. On the contrary, fasting and postprandial ratings of fullness and postprandial PYY3-36 increased in HIGH (P < 0.001 vs. CON). Ad libitum lunch energy intake remained unchanged over the course of the intervention. In both exercise groups, plasma ghrelin increased in relation to acute exercise after training. Thus neither moderate nor high doses of daily endurance exercise increased fasting and postprandial measures of appetite, but a high dose of exercise was associated with an increase in fasting and meal-related ratings of fullness and satiety.

Topics: Adult; Appetite; Appetite Regulation; Blood Glucose; Energy Intake; Exercise; Fasting; Fatty Acids, Nonesterified; Ghrelin; Glucagon; Glycerol; Humans; Insulin; Male; Overweight; Peptide Fragments; Peptide YY; Postprandial Period; Sedentary Behavior; Weight Loss; Young Adult

The long-term results of Roux-en-$\\hbox{Y}$ gastric bypass (gastric bypass) and vertical banded gastroplasty (VBG) from randomized studies have not been described in detail.. Patients were randomized to gastric bypass or VBG. Body mass index (BMI), body composition, eating habits and gastrointestinal hormones were reviewed after 6 years. The frequency of reoperation was assessed up to 10 years after surgery.. Sixty-six (80 per cent) of the 82 subjects randomized were assessed for weight and BMI 6 years after surgery, 30 (81 per cent) in the gastric bypass group and 36 (80 per cent) in the VBG group. Intention-to-treat analysis demonstrated greater weight loss after gastric bypass compared with VBG, 6 years after surgery: BMI reduced from 41·8 (95 per cent confidence interval 41·3 to 42·3) to 30·3 (28·6 to 32·0) kg/m(2) for gastric bypass and from 42·3 (42·8 to 44·8) to 32·9 (31·3 to 34·5) kg/m(2) for VBG (P = 0·036). Gastric bypass caused a larger loss of fat mass (P = 0·026) and better preservation of lean tissue (P = 0·009). Patients having a gastric bypass had greater postprandial responses to the satiety hormones glucagon-like peptide 1 and peptide YY (P = 0·003 and P = 0·004 respectively). Ghrelin levels did not differ between the groups. Patients with a gastric bypass maintained a lower intake of fat compared with those having VBG (P = 0·013). Some 89 per cent of patients who initially had VBG had undergone, or were scheduled for, conversion to gastric bypass at latest follow-up.. Gastric bypass was superior to VBG regarding weight loss, body composition, dietary composition and postprandial satiety hormone responses.

Topics: Body Mass Index; Eating; Female; Gastric Bypass; Gastroplasty; Ghrelin; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Obesity, Morbid; Peptide YY; Reoperation; Weight Loss

The mechanisms of amelioration of glycemic control early after laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) are not fully understood.. In this prospective, randomized 1-year trial, outcomes of LRYGB and LSG patients were compared, focusing on possibly responsible mechanisms. Twelve patients were randomized to LRYGB and 11 to LSG. These non-diabetic patients were investigated before and 1 week, 3 months, and 12 months after surgery. A standard test meal was given after an overnight fast, and blood samples were collected before, during, and after food intake for hormone profiles (cholecystokinin (CCK), ghrelin, glucagon-like peptide 1 (GLP-1), peptide YY (PYY)).. In both groups, body weight and BMI decreased markedly and comparably leading to an identical improvement of abnormal glycemic control (HOMA index). Post-surgery, patients had markedly increased postprandial plasma GLP-1 and PYY levels (p < 0.05) with ensuing improvement in glucose homeostasis. At 12 months, LRYGB ghrelin levels approached preoperative values. The postprandial, physiologic fluctuation returned, however, while LSG ghrelin levels were still markedly attenuated. One year postoperatively, CCK concentrations after test meals increased less in the LRYGB group than they did in the LSG group, with the latter showing significantly higher maximal CCK concentrations (p < 0.012 vs. LRYGB).. Bypassing the foregut is not the only mechanism responsible for improved glucose homeostasis. The balance between foregut (ghrelin, CCK) and hindgut (GLP-1, PYY) hormones is a key to understanding the underlying mechanisms.

Topics: Adult; Blood Glucose; Cholecystokinin; Female; Gastric Bypass; Gastrointestinal Hormones; Gastroplasty; Ghrelin; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Laparoscopy; Male; Obesity, Morbid; Peptide YY; Postprandial Period; Prospective Studies; Weight Loss

Laparoscopic Roux-en Y-Gastric bypass (LRYGBP) is the commonest available option for the surgical treatment of morbid obesity. Weight loss following bariatric surgery has been linked to changes of gastrointestinal peptides, shown to be implicated also in metabolic effects and appetite control. The purpose of this study was to evaluate whether gastric fundus resection in patients undergoing LRYGBP enhances the efficacy of the procedure in terms of weight loss, glucose levels, and hormonal secretion.. Twelve patients underwent LRYGBP and 12 patients LRYGBP plus gastric fundus resection (LRYGBP+FR). All patients were evaluated before and at 3, 6, and 12 months postoperatively. Blood samples were collected after an overnight fast and 30, 60, and 120 min after a standard 300-kcal mixed meal.. Body weight and body mass index decreased markedly and comparably after both procedures. Fasting ghrelin decreased 3 months after LRYGBP, but increased at 12 months to levels higher than baseline while after LRYGBP+FR was markedly and persistently decreased. Postprandial GLP-1, PYY, and insulin responses were enhanced more and postprandial glucose levels were lower after LRYGBP+FR compared to LRYGBP. Postoperatively, ghrelin changes correlated negatively with GLP-1 changes.. Resection of the gastric fundus in patients undergoing LRYGBP was associated with persistently lower fasting ghrelin levels; higher postprandial PYY, GLP-1, and insulin responses; and lower postprandial glucose levels compared to LRYGBP. These findings suggest that fundus resection in the setting of LRYGBP may be more effective than RYGBP for the management of morbid obesity and diabetes type 2.

Topics: Biomarkers; Body Mass Index; Diabetes Mellitus, Type 2; Fasting; Female; Gastric Bypass; Gastric Fundus; Ghrelin; Glucagon-Like Peptide 1; Humans; Male; Obesity, Morbid; Peptide YY; Postprandial Period; Weight Loss

The aim of this study was to examine changes in fasting total peptide YY (PYY) and ghrelin in nonobese premenopausal women after an exercise and diet program with and without weight loss.. Body composition, energy balance parameters, ghrelin, and PYY were measured before and after a 3-month intervention in nonexercising controls (n = 7) and exercising women who either remained weight stable (n = 5) or lost weight (n = 10). At baseline, subjects were 20.6 ± 2.2 yr, weighed 58.0 ± 4.8 kg, and had 27.2% ± 4.9% body fat. Supervised exercise training occurred five times a week for up to 90 min at 70%-80% of maximum HR. Subjects were fed a controlled diet.. Body weight (-3.2 ± 0.8 kg) and fat mass (-2.6 ± 0.7 kg) decreased significantly in the weight-loss exercise group. Neither fasting ghrelin nor PYY changed in response to exercise training in the absence of weight loss, and PYY did not change with exercise and weight loss. Fasting ghrelin did reveal a significant time × experimental group interaction (P = 0.025). The change in ghrelin was inversely correlated with the change in body weight, body mass index, fat-free mass, and energy availability.. Neither fasting ghrelin nor fasting PYY seem to play a role in the adaptive changes associated with exercise training when exercise occurs in the absence of weight loss. Fasting ghrelin concentrations increase when body weight is lost and may respond to even smaller changes in energy availability. However, fasting PYY does not seem to play a key role in the regulation of energy balance during diet- and exercise-associated weight loss.

Topics: Adipose Tissue; Adolescent; Adult; Body Weight; Diet; Energy Metabolism; Exercise; Female; Ghrelin; Humans; Peptide YY; Weight Loss; Young Adult

The SHAPE (Screened Health Assessment and Pacer Evaluation) trial was a 24 month randomized multicenter placebo-controlled study to determine the efficacy of an implantable gastric stimulator (IGS) for weight loss. This report is an investigator-initiated sub-study at one site designed to assess whether IGS affects plasma levels of ghrelin and peptide YY (PYY). The device was implanted in all subjects but was activated in the TREATMENT group (n = 7, BMI = 41.5 ± 2.0 kg/m2) and remained inactive in the CONTROL (n = 6, BMI = 39.5 ± 1.7 kg/m2) during the first 12 months. IGS was activated in both groups during months 12-24. Fasting venous blood was drawn at months 0, 12, and 24 and an oral glucose tolerance test (OGTT) was performed at month 12. Although there was no difference in weight loss at 6 months (. -6.6 ± 1.5% vs.. -6.2 ± 1.4%), at 24 months the CONTROL group exhibited weight gain from baseline (+2.2 ± 1.5%) that was significantly different from the weight loss in the TREATMENT group (-1.9 ± 1.4%; P < 0.05). At 12 months, fasting ghrelin was significantly increased (P < 0.05) in the TREATMENT group (285 ± 35 to 336 ± 35 pg/ml; weight change, -4.9 ± 1.4%), but not in the CONTROL (211 ± 36 to 208 ± 35 pg/ml; weight change, -3.4 ± 1.5%). No significant change was observed in postprandial suppression of plasma ghrelin or in fasting and postprandial PYY levels. In conclusion, IGS does not prevent the increase in fasting plasma ghrelin levels associated with weight loss. Further studies are needed to determine whether changes in technology can improve weight loss and maintenance, perhaps using gut hormones as biomarkers of possible efficacy.

Topics: Adolescent; Adult; Aged; Double-Blind Method; Electric Stimulation; Electrodes, Implanted; Fasting; Female; Ghrelin; Glucose Tolerance Test; Humans; Male; Middle Aged; Obesity, Morbid; Peptide YY; Postprandial Period; Weight Gain; Weight Loss; Young Adult

After weight loss, changes in the circulating levels of several peripheral hormones involved in the homeostatic regulation of body weight occur. Whether these changes are transient or persist over time may be important for an understanding of the reasons behind the high rate of weight regain after diet-induced weight loss.. We enrolled 50 overweight or obese patients without diabetes in a 10-week weight-loss program for which a very-low-energy diet was prescribed. At baseline (before weight loss), at 10 weeks (after program completion), and at 62 weeks, we examined circulating levels of leptin, ghrelin, peptide YY, gastric inhibitory polypeptide, glucagon-like peptide 1, amylin, pancreatic polypeptide, cholecystokinin, and insulin and subjective ratings of appetite.. Weight loss (mean [±SE], 13.5±0.5 kg) led to significant reductions in levels of leptin, peptide YY, cholecystokinin, insulin (P<0.001 for all comparisons), and amylin (P=0.002) and to increases in levels of ghrelin (P<0.001), gastric inhibitory polypeptide (P=0.004), and pancreatic polypeptide (P=0.008). There was also a significant increase in subjective appetite (P<0.001). One year after the initial weight loss, there were still significant differences from baseline in the mean levels of leptin (P<0.001), peptide YY (P<0.001), cholecystokinin (P=0.04), insulin (P=0.01), ghrelin (P<0.001), gastric inhibitory polypeptide (P<0.001), and pancreatic polypeptide (P=0.002), as well as hunger (P<0.001).. One year after initial weight reduction, levels of the circulating mediators of appetite that encourage weight regain after diet-induced weight loss do not revert to the levels recorded before weight loss. Long-term strategies to counteract this change may be needed to prevent obesity relapse. (Funded by the National Health and Medical Research Council and others; ClinicalTrials.gov number, NCT00870259.).

Topics: Body Mass Index; Body Weight; Cholecystokinin; Diet, Reducing; Female; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Intention to Treat Analysis; Leptin; Male; Middle Aged; Obesity; Peptide YY; Peptides; Postmenopause; Weight Loss

There have been reports of an inverse relationship between meal frequency (MF) and adiposity. It has been postulated that this may be explained by favourable effects of increased MF on appetite control and possibly on gut peptides as well. The main goal of the present study was to investigate whether using a high MF could lead to a greater weight loss than that obtained with a low MF under conditions of similar energy restriction. Subjects were randomised into two treatment arms (high MF = 3 meals+3 snacks/d or low MF = 3 meals/d) and subjected to the same dietary energy restriction of - 2931 kJ/d for 8 weeks. Sixteen obese adults (n 8 women and 8 men; age 34.6 (sd 9.5); BMI 37.1 (sd 4.5) kg/m2) completed the study. Overall, there was a 4.7 % decrease in body weight (P < 0.01); similarly, significant decreases were noted in fat mass ( - 3.1 (sd 2.9) kg; P < 0.01), lean body mass ( - 2.0 (sd 3.1) kg; P < 0.05) and BMI ( - 1.7 (sd 0.8) kg/m2; P < 0.01). However, there were NS differences between the low- and high-MF groups for adiposity indices, appetite measurements or gut peptides (peptide YY and ghrelin) either before or after the intervention. We conclude that increasing MF does not promote greater body weight loss under the conditions described in the present study.

Topics: Adipose Tissue; Adiposity; Adult; Appetite; Body Mass Index; Diet, Reducing; Eating; Feeding Behavior; Female; Ghrelin; Humans; Male; Middle Aged; Peptide YY; Time Factors; Weight Loss

The goal of this study was to understand the mechanisms of greater weight loss by gastric bypass (GBP) compared to gastric banding (GB) surgery. Obese weight- and age-matched subjects were studied before (T0), after a 12 kg weight loss (T1) by GBP (n = 11) or GB (n = 9), and at 1 year after surgery (T2). peptide YY(3-36) (PYY(3-36)), ghrelin, glucagon-like peptide-1 (GLP-1), leptin, and amylin were measured after an oral glucose challenge. At T1, glucose-stimulated GLP-1 and PYY levels increased significantly after GBP but not GB. Ghrelin levels did not change significantly after either surgery. In spite of equivalent weight loss, leptin and amylin decreased after GBP, but not after GB. At T2, weight loss was greater after GBP than GB (P = 0.003). GLP-1, PYY, and amylin levels did not significantly change from T1 to T2; leptin levels continued to decrease after GBP, but not after GB at T2. Surprisingly, ghrelin area under the curve (AUC) increased 1 year after GBP (P = 0.03). These data show that, at equivalent weight loss, favorable GLP-1 and PYY changes occur after GBP, but not GB, and could explain the difference in weight loss at 1 year. Mechanisms other than weight loss may explain changes of leptin and amylin after GBP.

Topics: Adult; Amyloid; Appetite Regulation; Follow-Up Studies; Gastric Bypass; Gastroplasty; Ghrelin; Glucagon-Like Peptide 1; Hormones; Humans; Islet Amyloid Polypeptide; Leptin; Metabolome; Middle Aged; Peptide YY; Time Factors; Weight Loss

Rodent studies show that oligofructose promotes weight loss, stimulates satiety hormone secretion, reduces energy intake, and improves lipid profiles.. Our objective was to examine the effects of oligofructose supplementation on body weight and satiety hormone concentrations in overweight and obese adults.. This study was a randomized, double-blind, placebo-controlled trial. Forty-eight otherwise healthy adults with a body mass index (in kg/m2) > 25 were randomly assigned to receive 21 g oligofructose/d or a placebo (maltodextrin) for 12 wk. Body composition (by dual-energy X-ray absorptiometry); meal tolerance tests, including satiety hormone response; food intake; and subjective appetite ratings were determined.. There was a reduction in body weight of 1.03 +/- 0.43 kg with oligofructose supplementation, whereas the control group experienced an increase in body weight of 0.45 +/- 0.31 kg over 12 wk (P = 0.01). A lower area under the curve (AUC) for ghrelin (P = 0.004) and a higher AUC for peptide YY (PYY) with oligofructose (P = 0.03) coincided with a reduction in self-reported caloric intake (P < or = 0.05). Glucose decreased in the oligofructose group and increased in the control group between initial and final tests (P < or = 0.05). Insulin concentrations mirrored this pattern (P < or = 0.05). Oligofructose supplementation did not affect plasma active glucagon-like peptide 1 secretion. According to a visual analog scale designed to assess side effects, oligofructose was well tolerated.. Independent of other lifestyle changes, oligofructose supplementation has the potential to promote weight loss and improve glucose regulation in overweight adults. Suppressed ghrelin and enhanced PYY may contribute in part to the reduction in energy intake. The trial was registered at clinicaltrials.gov as NCT00522353.

Topics: Adult; Area Under Curve; Blood Glucose; Dietary Supplements; Energy Intake; Female; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin; Male; Middle Aged; Obesity; Oligosaccharides; Overweight; Peptide YY; Weight Loss

To examine the effect of an equivalent weight loss, by gastric bypass surgery (GBP) or by diet, on peptide YY3-36 (PYY3-36), ghrelin, and leptin levels and to determine the effect of diabetes status on PYY3-36 levels.. The increased PYY3-36 levels after GBP may be involved in the magnitude and the sustainability of weight loss after surgery.. Of the 30 morbidly obese women who participated in the study, 21 had type 2 diabetes mellitus, and were studied before and after equivalent weight loss of 10 kg by either GBP (n = 11) or by diet (n = 10).. : PYY3-36 levels were higher in obese diabetic as compared with nondiabetic individuals (64.1 +/- 34.4 pg/mL vs. 39.9 +/- 21.1 pg/mL; P < 0.05). PYY3-36 levels increased markedly in response to oral glucose after GBP (peak: 72.3 +/- 20.5 pg/mL-132.7 +/- 49.7 pg/mL; P < 0.001; AUC0-180: 51.5 +/- 23.3 pg/mL x min-91.1 +/- 32.2 pg/mL x min P < 0.001), but not after diet (peak: 85.5 +/- 51.9 pg/mL-84.8 +/- 41.13 pg/mL; P = NS; AUC0-180: 68.3 +/- 38.5 pg/mL x min-61.1 +/- 42.2 pg/mL.min P = NS). Fasting ghrelin levels increased after diet (425 +/- 91 pg/mL-519 +/- 105 pg/mL; P < 0.05), but did not change after GBP (506 +/- 121 pg/mL-482 +/- 196 pg/mL; P = NS).. Diabetes status seems to be a determinant of PYY3-36 levels. GBP, but not diet-induced weight loss, resulted in markedly increased glucose-stimulated PYY3-36 levels. The increase in stimulated PYY3-36 levels after GBP is likely a result of the surgery rather than a secondary outcome of weight loss. Changes in PYY3-36 levels and ghrelin could contribute to the success of GBP in sustaining weight loss.

Topics: Adult; Body Mass Index; Caloric Restriction; Cohort Studies; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Ghrelin; Humans; Leptin; Middle Aged; Obesity, Morbid; Peptide Fragments; Peptide YY; Weight Loss

Bariatric surgery is currently the most effective treatment in morbidly obese patients, leading to durable weight loss.. In this prospective double blind study, we aim to evaluate and compare the effects of laparoscopic Roux-en-Y gastric bypass (LRYGBP) with laparoscopic sleeve gastrectomy (LSG) on body weight, appetite, fasting, and postprandial ghrelin and peptide-YY (PYY) levels.. After randomization, 16 patients were assigned to LRYGBP and 16 patients to LSG. Patients were reevaluated on the 1st, 3rd, 6th, and 12th postoperative month. Blood samples were collected after an overnight fast and in 6 patients in each group after a standard 420 kcal mixed meal.. Body weight and body mass index (BMI) decreased markedly (P < 0.0001) and comparably after either procedure. Excess weight loss was greater after LSG at 6 months (55.5% +/- 7.6% vs. 50.2% +/- 6.5%, P = 0.04) and 12 months (69.7% +/- 14.6% vs. 60.5% +/- 10.7%, [P = 0.05]). After LRYGBP fasting ghrelin levels did not change significantly compared with baseline (P = 0.19) and did not decrease significantly after the test meal. On the other hand, LSG was followed by a marked reduction in fasting ghrelin levels (P < 0.0001) and a significant suppression after the meal. Fasting PYY levels increased after either surgical procedure (P < or = 0.001). Appetite decreased in both groups but to a greater extend after LSG.. PYY levels increased similarly after either procedure. The markedly reduced ghrelin levels in addition to increased PYY levels after LSG, are associated with greater appetite suppression and excess weight loss compared with LRYGBP.

Topics: Appetite; Bariatric Surgery; Double-Blind Method; Gastrectomy; Gastric Bypass; Ghrelin; Humans; Peptide YY; Prospective Studies; Weight Loss

The beneficial effects of metformin in patients with type 2 diabetes mellitus (T2DM) and polycystic ovarian syndrome (PCOS) are thought to be in part due to weight reduction. However, the mechanisms by which metformin causes weight loss are unclear. We sought to determine whether circulating levels of the anorectic gut hormone peptide tyrosine tyrosine (PYY) show any correlation with metformin-induced weight loss.. We examined the acute effects of orally administrated metformin on fasting PYY levels in eight healthy normal-weight female subjects. Subsequently, we evaluated the effects of 6 months metformin treatment on fasting PYY levels and anthropometric measurements in 20 women with PCOS.. In normal-weight females 10 days' metformin treatment increased fasting PYY levels (P < 0.01). Similarly, in PCOS subjects metformin treatment increased fasting PYY concentrations (P < 0.05). In both groups a marked variation in PYY increase in response to metformin was observed. Long-term metformin treatment was associated with improvements in weight (P < 0.05), BMI (P < 0.05), fasting glucose (P < 0.05) and menstrual frequency (P < 0.01). Interestingly, change in PYY levels were correlated with change in waist circumference (r = 0.55, P < 0.05).. Acute and chronic oral metformin administration increase fasting PYY levels and may contribute to metformin's weight loss effect. Further studies are now required to clarify whether changes in circulating PYY levels in response to metformin treatment can be used to predict which patients will subsequently lose weight long-term and gain cycle restoration.

Topics: Adult; Fasting; Female; Humans; Metformin; Peptide YY; Polycystic Ovary Syndrome; Waist Circumference; Weight Loss

The gastrointestinal peptide hormone, peptide YY(3-36) (PYY(3-36)), is implicated to be a postprandial satiety factor.. The aim of this study is to assess the safety, tolerability, and efficacy of intranasal PYY(3-36) to induce weight loss in obese patients.. The study was designed as a randomized, 2-wk, single-blind placebo run-in followed by a 12-wk double-blind, placebo-controlled treatment period.. The study was set within a private and institutional practice.. A total of 133 obese patients (body mass index, 30-43 kg/m(2); age, 18-65 yr) participated in the study.. Placebo or 200- or 600-microg PYY(3-36) was administered as an intranasal spray 20 min before breakfast, lunch, and dinner in conjunction with a hypocaloric diet and exercise.. Body weight was the main outcome measure.. The number of patients completing 12 wk on the drug was 38 of 43 (88%), 31 of 44 (70%), and 12 of 46 (26%) for placebo, 200 microg three times a day (t.i.d.) and 600 microg t.i.d., respectively. In the 600 microg t.i.d. group, 27 of 46 (59%) patients discontinued due to nausea and vomiting. Among all randomized patients who took at least one drug dose and had a postbaseline measurement, the mean body weight change from baseline was -2.8, -3.7, and -1.4 kg for placebo, 200 and 600 microg, respectively. The least squares mean difference (95% confidence interval) between placebo and 200 microg was -0.9 (-2.6, 0.7) kg (P = 0.251). A difference of 2.11 kg was sought. No meaningful inference can be drawn from the few patients who completed the study on 600 microg.. Intranasal PYY(3-36) as administered at these intervention doses and preprandial timing is not efficacious in inducing weight loss in obese patients after 12 wk of treatment.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Body Mass Index; Body Weight; Diet, Reducing; Dose-Response Relationship, Drug; Double-Blind Method; Exercise Therapy; Female; Humans; Male; Middle Aged; Obesity; Peptide Fragments; Peptide YY; Treatment Outcome; Weight Loss

To evaluate the physiologic importance of the satiety gut hormones.. Controversy surrounds the physiologic role of gut hormones in the control of appetite. Bariatric surgery remains the most effective treatment option for obesity, and gut hormones are implicated in the reduction of appetite and weight after Roux-en-Y gastric bypass.. We correlated peptide YY (PYY) and glucagon-like peptide 1 (GLP-1) changes within the first week after gastric bypass with changes in appetite. We also evaluated the gut hormone responses of patients with good or poor weight loss after gastric bypass. Finally, we inhibited the gut hormone responses in gastric bypass patients and then evaluated appetite and food intake.. Postprandial PYY and GLP-1 profiles start rising as early as 2 days after gastric bypass (P < 0.05). Changes in appetite are evident within days after gastric bypass surgery (P < 0.05), and unlike other operations, the reduced appetite continues. However, in patients with poor weight loss after gastric bypass associated with increased appetite, the postprandial PYY and GLP-1 responses are attenuated compared with patients with good weight loss (P < 0.05). Inhibiting gut hormone responses, including PYY and GLP-1 after gastric bypass, results in return of appetite and increased food intake (P < 0.05).. The attenuated appetite after gastric bypass is associated with elevated PYY and GLP-1 concentrations, and appetite returns when the release of gut hormones is inhibited. The results suggest a role for gut hormones in the mechanism of weight loss after gastric bypass and may have implications for the treatment of obesity.

Topics: Appetite Regulation; Body Mass Index; Female; Follow-Up Studies; Gastric Bypass; Ghrelin; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Obesity, Morbid; Peptide YY; Prospective Studies; Treatment Outcome; Weight Loss

The aim of this study was to compare changes in gastrointestinal hormones and appetite ratings after a similar weight loss induced by a very low-energy diet alone or in combination with sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB).. Patients with severe obesity scheduled for SG (n = 15) and RYGB (n = 14) and 15 controls (very low-energy diet alone) were recruited. Body weight/composition, plasma concentrations of ß-hydroxybutyric acid, acylated ghrelin, total glucagon-like peptide-1, total peptide YY, cholecystokinin, and ratings of hunger, fullness, desire to eat, and prospective food consumption were measured pre- and postprandially, before and after 10 weeks of intervention.. Changes in body weight/composition and level of ketosis were similar across groups. In SG and RYGB, basal and postprandial acylated ghrelin declined, and postprandial glucagon-like peptide-1 increased, both significantly more compared with controls. Postprandial peptide YY increased in all groups. Overall, postprandial hunger decreased, and postprandial fullness increased. But ratings of desire to eat and prospective food consumption were more favorable after both surgeries compared with controls.. Weight loss with SG and RYGB leads to more favorable changes in gastrointestinal hormones compared with diet alone, although ratings of appetite were reduced across all groups.

Topics: Appetite; Diet; Gastrectomy; Gastric Bypass; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Obesity, Morbid; Peptide YY; Weight Loss

The role of fat-free mass loss (FFML) in modulating weight regain in individuals with obesity, as well as the potential mechanisms involved, remain inconsistent.. The aim of this study was to determine if % FFML following weight loss (WL) is a predictor of weight regain and to investigate the association between %FFML and changes in appetite markers.. WL at week 9 was 17.5 ± 4.3kg and %FFML 20.4 ± 10.6%. Weight regain at 1 y was 1.7 ± 8.2 kg (8.8 ± 45.0%). After adjusting for WL and fat mass at baseline, %FFML at week 9 was not a significant predictor of weight regain. Similar results were seen at week 13. The greater the %FFML at week 9, but not 13, the smaller the reduction, or greater the increase in basal ghrelin concentration (β: -3.2; 95% CI: -5.0, -1.1; P = 0.003), even after adjusting for WL and β-hydroxybutyrate.. %FFML was not a significant predictor of weight regain at 1 y in individuals with obesity. However, a greater %FFML was accompanied by a greater increase in ghrelin secretion under ketogenic conditions, suggesting a link between fat-free mass and appetite regulation. This trial was registered at clinicaltrials.gov as NCT01834859.

Topics: 3-Hydroxybutyric Acid; Adult; Appetite; Ghrelin; Humans; Male; Middle Aged; Obesity; Peptide YY; Weight Gain; Weight Loss

Bariatric surgery and pharmacology treatments increase circulating glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), in turn promoting satiety and body weight (BW) loss. However, the utility of GLP-1 and PYY in predicting appetite response during dietary interventions remains unsubstantiated. This study investigated whether the decrease in hunger observed following low energy diet (LED)-induced weight loss was associated with increased circulating 'satiety peptides', and/or associated changes in glucose, glucoregulatory peptides or amino acids (AAs). In total, 121 women with obesity underwent an 8-week LED intervention, of which 32 completed an appetite assessment via a preload challenge at both Week 0 and Week 8, and are reported here. Visual analogue scales (VAS) were administered to assess appetite-related responses, and blood samples were collected over 210 min post-preload. The area under the curve (AUC

Topics: Amino Acids; Appetite; Biomarkers; Female; Ghrelin; Glucagon-Like Peptide 1; Humans; Peptide YY; Weight Loss

Mechanisms underlying long-term sustained weight loss and glycemic normalization after obesity surgery include changes in gut hormone levels, including glucagon-like peptide 1 (GLP-1) and peptide YY (PYY). We demonstrate that two peptide biased agonists (GEP44 and GEP12) of the GLP-1, neuropeptide Y1, and neuropeptide Y2 receptors (GLP-1R, Y1-R, and Y2-R, respectively) elicit Y1-R antagonist-controlled, GLP-1R-dependent stimulation of insulin secretion in both rat and human pancreatic islets, thus revealing the counteracting effects of Y1-R and GLP-1R agonism. These agonists also promote insulin-independent Y1-R-mediated glucose uptake in muscle tissue ex vivo and more profound reductions in food intake and body weight than liraglutide when administered to diet-induced obese rats. Our findings support a role for Y1-R signaling in glucoregulation and highlight the therapeutic potential of simultaneous receptor targeting to achieve long-term benefits for millions of patients.

Topics: Animals; Glucagon-Like Peptide 1; Glycemic Control; Humans; Neuropeptides; Peptide YY; Rats; Weight Loss

Bariatric surgery has been widely recognized as the most efficient long-term treatment method in severe obesity, yet therapy success shows considerable interindividual variability. Postoperative metabolic adaptations, including improved gut hormone secretion (GLP-1, PYY and ghrelin), and restored executive function may play an explanatory role in weight loss, yet causes for poor success in individual patients remain unknown. This study investigates gut-hormonal and cognitive characteristics in extreme weight loss responders to bariatric surgery.. Patients (n = 47) with high or low excessive weight loss (EWL) at least 2 years after Roux-en-Y-gastric bypass or sleeve gastrectomy were allocated into good responders (GR, EWL 82.4 ± 11.6%) and poor responders (PR, EWL 24.0 ± SD 12.8%) to study differences in postprandial secretion of GLP-1, PYY, ghrelin and in working memory (WM).. Mean BMI was 47.1 ± 6.2 kg/m² in PR (n = 21) and 28.9 ± 3.1 kg/m² in GR (n = 26, p < 0.001). Fasted GLP-1 and PYY were comparable for GR and PR (p > 0.2) and increased strongly after a standardized test meal (300 kcal liquid meal) with a peak at 15 to 30 min. The increase was stronger in GR compared to PR (GLP-1, PYY: Time x Group p < 0.05). Plasma ghrelin levels already differed between groups at fasted state, showing significantly higher levels for GR (p < 0.05). Postprandially, ghrelin secretion was suppressed in both groups, but suppression was higher in GR (Time x Group p < 0.05). GR showed significantly higher WM scores than PR (p < 0.05). Postprandial ghrelin (iAUC), but not GLP-1 or PYY plasma levels, significantly mediated the relationship between EWL and a WM subscore (IS score, CI = 0.07 - 1.68), but not WM main score (MIS score, CI = -0.07 - 1.54), in mediation analyses.. Excess weight loss success after bariatric surgical procedures is associated with distinct profiles of gut-hormones at fasted and postprandial state, and differences in working memory. Better working memory performance in GR might be mediated by higher postprandial reduction in ghrelin plasma levels. Future studies need to integrate longitudinal data, larger samples and more sensitive cognitive tests.

Topics: Bariatric Surgery; Cognition; Gastric Bypass; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Peptide YY; Weight Loss

After Roux-en-Y gastric bypass (RYGB) a subset of patients never obtain excess BMI loss (EBMIL) > 50% and are categorized as having primary weight loss (WL) failure. We hypothesized that postprandial concentrations of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) would be lower in patients with primary WL failure compared with patients with successfully maintained WL. Furthermore, that inhibition of gut hormone secretions would increase ad libitum food intake less in patients with primary WL failure.. Twenty women with primary WL failure (LowEBMIL < 50%) were individually matched to twenty women with successful WL (HighEBMIL > 60%) on age, preoperative BMI and time from RYGB. On separate days performed in a random order, patient-blinded subcutaneous injections of octreotide or saline (placebo) were followed by a fixed breakfast and an ad libitum lunch with blood sampling for appetite regulating hormones and Visual-Analogue-Scale (VAS)-scoring of hunger/satiety. Furthermore, participants underwent gene variant analysis for GLP-1, PYY and their receptors, indirect calorimetry, dual-energy X-ray absorptiometry (DXA)-scans, 4-days at-home food registration and 14-days step counting.. On placebo days, postprandial GLP-1, PYY and cholecystokinin (CCK) concentrations were similar between groups after breakfast. Fasting ghrelin was lower in LowEBMIL, but the postprandial suppression was similar. LowEBMIL had lower satiety VAS-scores and less suppression of hunger VAS-scores. Gene variants did not differ between groups. Octreotide diminished GLP-1, PYY, CCK and ghrelin concentrations in both groups. Octreotide did not affect ad libitum food intake in LowEBMIL (-1% [-13, 12], mean [95%CI]), while food intake increased in HighEBMIL (+23% [2,44]).. Primary WL failure after RYGB was not characterized by impaired secretions of appetite regulating gut hormones. Interestingly, inhibition of gut hormone secretions with octreotide only increased food intake in patients with successful WL post-RYGB. Thus, an impaired central anorectic response to gut hormones may contribute to primary WL failure after RYGB.

Topics: Cholecystokinin; Eating; Female; Gastric Bypass; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Octreotide; Peptide YY; Weight Loss

Weight loss is associated with a disproportionate reduction in energy expenditure, along with increases in hunger feelings and ghrelin concentrations. These changes are presumed to be homeostatic mechanisms to counteract the energy deficit. The possibility that these 2 components of the energy balance equation are mechanistically linked has never been examined.. This study aimed to determine if the disproportionate reduction in resting metabolic rate (RMR) seen with weight loss is associated with changes in the plasma concentration of gastrointestinal hormones involved in appetite regulation and subjective appetite ratings.. This was a longitudinal study with repeated measurements. Fifty-six individuals with obesity (body mass index [BMI]: 34.5±0.5 kg/m. A 14.2±0.6 kg weight loss was seen at Wk9 and maintained at Wk13. RQ was significantly reduced at Wk9 (0.82±0.06 vs. 0.76±0.05, P< 0.001) but returned to baseline at Wk13. Metabolic adaptation was seen at Wk9, but not Wk13 (-341±58, P <0.001 and -75±72 kJ/d, P = 0.305, respectively). The larger the difference between measured and predicted RMR at both timepoints, the greater the increase in hunger, desire to eat, and composite appetite score (fasting and postprandial at Wk9, postprandial only at Wk13), even after adjusting for weight loss and RQ.. A larger metabolic adaptation during weight loss is accompanied by a greater drive to eat. This might help explain the interindividual differences in weight loss outcomes to dietary interventions.

Topics: Appetite; Ghrelin; Humans; Longitudinal Studies; Male; Middle Aged; Obesity; Peptide YY; Postprandial Period; Weight Loss

Mimetics of the anorexigenic gut hormone glucagon-like peptide 1 (GLP-1) were originally developed as insulinotropic anti-diabetic drugs but also evoke significant weight loss, leading to their recent approval as obesity therapeutics. Co-activation of receptors for GLP-1 and other gut hormones which reduce food intake - peptide YY (PYY

Topics: Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Glucagon-Like Peptide 1; Humans; Obesity; Peptide YY; Weight Loss

Obesity interventions often result in increased motivation to eat.. We investigated relationships between obesity outcomes and changes in brain activation by visual food cues and hormone levels in response to obesity intervention by family-based behavioral treatment (FBT).. Neuroimaging and hormone assessments were conducted before and after 24-week FBT intervention in children with obesity (OB, n = 28), or children of healthy weight without intervention (HW, n = 17), all 9- to 11-year-old boys and girls. We evaluated meal-induced changes in neural activation to high- vs low-calorie food cues across appetite-processing brain regions and gut hormones.. Among children with OB who underwent FBT, greater declines of BMI z-score were associated with lesser reductions after the FBT intervention in meal-induced changes in neural activation to high- vs low-calorie food cues across appetite-processing brain regions (P < 0.05), and the slope of relationship was significantly different compared with children of HW. In children with OB, less reduction in brain responses to a meal from before to after FBT was associated with greater meal-induced reduction in ghrelin and increased meal-induced stimulation in peptide YY and glucagon-like peptide-1 (all P < 0.05).. In response to FBT, adaptations of central satiety responses and peripheral satiety-regulating hormones were noted. After weight loss, changes of peripheral hormone secretion support weight loss, but there was a weaker central satiety response. The findings suggest that even when peripheral satiety responses by gut hormones are intact, the central regulation of satiety is disturbed in children with OB who significantly improve their weight status during FBT, which could favor future weight regain.

Topics: Behavior Therapy; Brain; Child; Family Relations; Female; Gastrointestinal Hormones; Ghrelin; Humans; Male; Obesity; Peptide YY; Postprandial Period; Satiety Response; Weight Loss

Biliopancreatic diversion with duodenal switch (BPD/DS) results in lifelong changes in gastrointestinal physiology with unclear associations with appetite perception.. To explore mixed meal-induced changes in glucose homeostasis and gut hormones and their correlations with appetite perception.. University hospital.. Of 28 patients studied preoperatively (age: 38.4 ± 11.3 years; body mass index [BMI]: 56.5 ± 5.1 kg/m. BPD/DS resulted in 66.1% ± 23.3% excess BMI loss. Leptin was halved. Glucose and insulin levels were reduced, blunting a preoperative peak at 30 minutes, giving a lower homeostasis model assessment for insulin resistance (HOMA-IR; 13.9 versus 4.8). In contrast, reduced ghrelin and motilin concentrations were accompanied by pronounced peaks 20-30 minutes prior to meal responses. GIP was reduced, whereas GLP-1 and PYY responses were markedly increased, with an early postprandial peak (P < .05, for all). HOMA-IR correlated with insulin (r = .72) and GIP (r = .57). Postoperatively, satiety correlated with GLP-1 (r = .56), whereas the gastric motility index correlated with the desire to eat (r = .60), percentage excess BMI loss (r = -.55), and percentage total weight loss (r = -.49). Delta insulin, GLP-1, and leptin correlated positively with percentage total weight loss (r = .51, r = .48, and r = .58, respectively).. BPD/DS reduces leptin, HOMA-IR, and GIP while markedly increasing GLP-1 and PYY. This study marks the magnitude change in GLP-1 with additional effects of PYY as important factors for weight loss.

Topics: Adult; Appetite; Biliopancreatic Diversion; Female; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Glucagon-Like Peptide 1; Glucose; Homeostasis; Humans; Insulin; Leptin; Male; Middle Aged; Motilin; Peptide YY; Weight Loss

There is a critical unmet need for therapeutics to treat the epidemic of comorbidities associated with obesity and type 2 diabetes, ideally devoid of nausea/emesis. This study developed monomeric peptide agonists of glucagon-like peptide 1 receptor (GLP-1R) and neuropeptide Y2 receptor (Y2-R) based on exendin-4 (Ex-4) and PYY

Topics: Animals; Binding, Competitive; Blood Glucose; Exenatide; Glucagon-Like Peptide-1 Receptor; Glucose; Humans; Insulin Secretion; Islets of Langerhans; Male; Microsomes, Liver; Models, Molecular; Molecular Docking Simulation; Nausea; Peptide YY; Rats; Rats, Sprague-Dawley; Receptors, Neuropeptide Y; Shrews; Structure-Activity Relationship; Vomiting; Weight Loss

Obesity is a complex disease associated with a high risk of comorbidities. Gastric bypass surgery, an invasive procedure with low patient eligibility, is currently the most effective intervention that achieves sustained weight loss. This beneficial effect is attributed to alterations in gut hormone signaling. An attractive alternative is to pharmacologically mimic the effects of bariatric surgery by targeting several gut hormonal axes. The G protein-coupled receptor 39 (GPR39) expressed in the gastrointestinal tract has been shown to mediate ghrelin signaling and control appetite, food intake, and energy homeostasis, but the broader effect on gut hormones is largely unknown. A potent and efficacious GPR39 agonist (Cpd1324) was recently discovered, but the in vivo function was not addressed. Herein we studied the efficacy of the GPR39 agonist, Cpd1324, on metabolism and gut hormone secretion.. Body weight, food intake, and energy expenditure in GPR39 agonist-treated mice and GPR39 KO mice were studied in calorimetric cages. Plasma ghrelin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and peptide YY (PYY) levels were measured. Organoids generated from murine and human small intestine and mouse colon were used to study GLP-1 and PYY release. Upon GPR39 agonist administration, dynamic changes in intracellular GLP-1 content were studied via immunostaining and changes in ion transport across colonic mucosa were monitored in Ussing chambers. The G protein activation underlying GPR39-mediated selective release of gut hormones was studied using bioluminescence resonance energy transfer biosensors.. The GPR39 KO mice displayed a significantly increased food intake without corresponding increases in respiratory exchange ratios or energy expenditure. Oral administration of a GPR39 agonist induced an acute decrease in food intake and subsequent weight loss in high-fat diet (HFD)-fed mice without affecting their energy expenditure. The tool compound, Cpd1324, increased GLP-1 secretion in the mice as well as in mouse and human intestinal organoids, but not in GPR39 KO mouse organoids. In contrast, the GPR39 agonist had no effect on PYY or GIP secretion. Transepithelial ion transport was acutely affected by GPR39 agonism in a GLP-1- and calcitonin gene-related peptide (CGRP)-dependent manner. Analysis of Cpd1324 signaling properties showed activation of Gα. The GPR39 agonist described in this study can potentially be used by oral administration as a weight-lowering agent due to its stimulatory effect on GLP-1 secretion, which is most likely mediated through a unique activation of Gα subunits. Thus, GPR39 agonism may represent a novel approach to effectively treat obesity through selective modulation of gastrointestinal hormonal axes.

Topics: Animals; Appetite Regulation; Bariatric Surgery; Body Weight; Eating; Enteroendocrine Cells; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Peptide YY; Receptors, G-Protein-Coupled; Receptors, Gastrointestinal Hormone; Weight Loss

Glycosuria induced by sodium-glucose cotransporter 2 (SGLT2) inhibitors leads to weight loss and improved diabetes control, but a significant disparity exists between observed and expected weight loss with these medications, hindering clinical effects. This study investigated whether this discrepancy could be explained by compensatory increases in appetite and associated alterations in appetite-regulating hormones.. This was a prospective single-center observational pilot study. Adults 18-70 years old newly prescribed an SGLT2 inhibitor through usual care were invited to participate. Fasting and postprandial appetite was assessed immediately before, 1 week after, and 12 weeks after SGLT2 inhibitor initiation. Serum samples were collected at corresponding time points to measure ghrelin, leptin, and peptide tyrosine-tyrosine (PYY). Seven patients were included. At 1 and 12 weeks after SGLT2 inhibitor initiation, self-reported appetite did not change significantly and trended toward a decrease in appetite. There were no significant differences in fasting or postprandial ghrelin, leptin, or PYY.. Results suggest the discrepancy between expected and observed weight loss with SGLT2 inhibitors cannot be explained by increases in appetite or changes in appetite-regulating hormones. Further studies are needed to investigate alternative metabolic compensatory mechanisms to optimize weight loss with SGLT2 inhibitor use.

Topics: Aged; Appetite Regulation; Biomarkers; Diabetes Mellitus, Type 2; Female; Ghrelin; Humans; Leptin; Male; Middle Aged; Peptide YY; Pilot Projects; Prospective Studies; Sodium-Glucose Transporter 2 Inhibitors; Time Factors; Treatment Outcome; Weight Loss

Alterations in several gastrointestinal hormones are implicated in the postoperative suppression of food intake leading to weight loss after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). The aim was to evaluate changes in responses of gastrointestinal hormones after RYGB and SG and the associations of these changes with weight loss, energy intake, and food preferences.. Forty-two subjects with severe obesity were included (32 RYGB; 10 SG). Postprandial responses of glicentin, oxyntomodulin, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and ghrelin were measured before and 6 months after surgery. Energy intake and energy density were assessed before and 6 months after surgery using a buffet meal test and weight loss was assessed 18 months after surgery.. Postprandial concentrations of glicentin, oxyntomodulin, GLP-1, and ghrelin differed between RYGB and SG (all P ≤ .02). Enhanced responses of glicentin and oxyntomodulin predicted a greater weight loss (both P < .01) and were associated with a larger decrease in energy density (P ≤ .04). No associations were found for GLP-1, PYY, and ghrelin, and changes were not associated with changes in energy intake. When combing all hormones, 60%, 19%, and 33% of the variations in weight loss, energy intake, and energy density, respectively, could be explained.. Postprandial responses of gastrointestinal hormones differed between RYGB and SG. Enhanced responses of glicentin and oxyntomodulin predicted a better weight loss and were associated with a decreased preference for energy-dense foods. Replication of these results could imply an opportunity to identify patients in need of additional support after surgical treatments of obesity.

Topics: Adult; Bariatric Surgery; Biomarkers; Case-Control Studies; Energy Intake; Female; Follow-Up Studies; Food Preferences; Gastrectomy; Gastric Bypass; Glicentin; Humans; Male; Obesity; Oxyntomodulin; Peptide YY; Prognosis; Weight Loss

Weight-loss maintenance is challenging, and few succeed in the long term. This study aimed to explain how appetite-related hormones, adaptive thermogenesis, perceived hunger and stress influence weight-loss maintenance.. Mean (SD) changes in body weight (-13.8 ± 6.3 kg) and total adipose tissue (-11.5 ± 4.9 kg) were significant (P < 0.001). Weight loss was associated with a significant reduction in resting metabolic rate (-291 ± 226 kcal/day, P < 0.001) and adaptive thermogenesis (-150 ± 162 kcal/day, P = 0.003), reduction in leptin (P < 0.001) and GLP-1 (P = 0.015), an increase in ghrelin (P < 0.001), and no changes in PYY and GDF-15. Weight regain between 6 and 24 months (6.1 ± 6.3 kg, P < 0.05) was negatively correlated with GLP-1 at baseline (r = −0.7, P = 0.003) and after weight loss (r = -0.7, P = 0.005). Participants did not report increased hunger after weight loss, and stress-related/emotional eating was perceived as the main reason for regain.. Weight regain is more likely with lower fasting GLP-1 at baseline and following weight loss, but psychological aspects of eating behaviour appear as important in attenuating weight-loss maintenance.

Topics: Adult; Appetite; Female; Ghrelin; Humans; Hunger; Middle Aged; Peptide YY; Thermogenesis; Weight Loss

To compare appetite markers in reduced-obese individuals with a nonobese control group.. A total of 34 adults with obesity who lost 17% body weight at week 13 and maintained this weight loss (WL) at 1 year were compared with 33 nonobese controls matched for body composition. Basal and postprandial subjective appetite ratings and appetite-related hormone concentrations (ghrelin, total peptide YY, peptide YY3-36, total and active glucagon-like peptide 1, and cholecystokinin) were measured in all participants and repeated at week 13 and 1 year in the weight-reduced group.. WL led to a reduction in prospective food consumption and an increase in feelings of hunger, fullness, and ghrelin secretion (basal and postprandial), but these new ratings were no different from those seen in controls. Postprandial concentrations of active glucagon-like peptide 1, total peptide YY, and cholecystokinin were lower in individuals with obesity at all time points compared with controls.. The increased drive to eat (both subjective feelings of hunger and ghrelin concentrations) seen in reduced-obese individuals, both after acute and sustained WL, reflects a normalization toward a lower body weight. Overall, WL does not have a sustained negative impact on satiety peptide secretion, despite a blunted secretion in individuals with obesity compared with nonobese controls.

Topics: Adult; Appetite; Body Mass Index; Body Weight; Cholecystokinin; Eating; Female; Ghrelin; Glucagon-Like Peptide 1; Homeostasis; Humans; Male; Middle Aged; Obesity; Peptide YY; Satiation; Weight Loss

The central mechanisms underlying the marked beneficial metabolic effects of bariatric surgery are unclear. Here, we characterized global gene expression in the hypothalamic arcuate nucleus (Arc) in diet-induced obese (DIO) rats following Roux-en-Y gastric bypass (RYGB). 60 days post-RYGB, the Arc was isolated by laser-capture microdissection and global gene expression was assessed by RNA sequencing. RYGB lowered body weight and adiposity as compared to sham-operated DIO rats. Discrete transcriptome changes were observed in the Arc following RYGB, including differential expression of genes associated with inflammation and neuropeptide signaling. RYGB reduced gene expression of glial cell markers, including Gfap, Aif1 and Timp1, confirmed by a lower number of GFAP immunopositive astrocyte profiles in the Arc. Sham-operated weight-matched rats demonstrated a similar glial gene expression signature, suggesting that RYGB and dietary restriction have common effects on hypothalamic gliosis. Considering that RYGB surgery also led to increased orexigenic and decreased anorexigenic gene expression, this may signify increased hunger-associated signaling at the level of the Arc. Hence, induction of counterregulatory molecular mechanisms downstream from the Arc may play an important role in RYGB-induced weight loss.

Topics: Adiposity; Animals; Arcuate Nucleus of Hypothalamus; Astrocytes; Biomarkers; Diet, High-Fat; Diet, Reducing; Eating; Gastric Bypass; Gene Expression Profiling; Gene Expression Regulation; Glial Fibrillary Acidic Protein; Gliosis; Glucagon-Like Peptide 1; Inflammation; Laser Capture Microdissection; Male; Neuropeptides; Obesity; Peptide YY; Rats; Rats, Sprague-Dawley; Sequence Analysis, RNA; Weight Loss

Sleeve gastrectomy with ileal transposition has been shown to be superior to sleeve gastrectomy alone for promoting weight loss in rat and porcine models. The absence of a mouse model for this procedure has impeded efforts to understand the molecular physiology underlying its efficacy. This study demonstrates the long-term survivability of sleeve gastrectomy with ileal transposition in mice.. In this study of technical feasibility, a sleeve gastrectomy with ileal transposition (SGIT), sleeve gastrectomy (SG), or sham surgery (SH) was performed on 7- to 8-week-old C57Bl/6J mice (n = 8 for each). To evaluate long-term survivability, mice were placed on an obesogenic diet and weighed weekly for 10 weeks. The intestinal identity of the transposed segment was assessed with gene expression analysis of duodenal-, jejunal-, and ileal-specific hormones using quantitative polymerase chain reaction.. Overall, SGIT better prevented weight gain than the SG or sham procedures (10-week post-operative weight: SH 45.3 ± 1.0 g, SG 41.25 ± 1.6 g, SGIT 35.4 ± 0.8 g). Gene expression pattern analysis of three markers of intestinal identity (gastrin, cholecystokinin, and peptide YY) suggests that the ileal identity of the transposed segment is maintained 10 weeks after transposition.. We demonstrate for the first time a reproducible mouse model of sleeve gastrectomy with ileal transposition. Future studies utilizing this model will expand our understanding of the molecular pathways through which the hindgut regulates satiety.

Topics: Animals; Biomarkers; Blood Glucose; Cholecystokinin; Disease Models, Animal; Feasibility Studies; Gastrectomy; Gastrins; Gene Expression; Ileum; Mice, Inbred C57BL; Peptide YY; Random Allocation; RNA; Weight Loss

The antidiabetic drug metformin causes weight loss, but the underlying mechanisms are unclear. Recent clinical studies show that metformin increases plasma levels of the anorectic gut hormone, peptide YY (PYY), but whether this is through a direct effect on the gut is unknown.. We hypothesized that exposure of human gut mucosal tissue to metformin would acutely trigger PYY secretion.. Mucosal tissue was prepared from 46 human colonic and 9 ileal samples obtained after surgical resection and ex vivo secretion assays were performed. Tissue was exposed to metformin, as well as a series of other compounds as part of our mechanistic studies, in static incubations. Supernatant was sampled after 15 minutes.. PYY levels in supernatant, measured using ELISA.. Metformin increased PYY secretion from both ileal (P < 0.05) and colonic (P < 0.001) epithelia. Both basal and metformin-induced PYY secretion were unchanged across body mass index or in tissues obtained from individuals with type 2 diabetes. Metformin-dependent PYY secretion was blocked by inhibitors of the plasma membrane monoamine transporter (PMAT) and the serotonin reuptake transporter (SERT), as well as by an inhibitor of AMP kinase (AMPK).. This is a report of a direct action of metformin on the gut epithelium to trigger PYY secretion in humans, occurring via cell internalization through PMAT and SERT and intracellular activation of AMPK. Our results provide further support that the role of metformin in the treatment of metabolic syndrome has a gut-based component.

Topics: Adult; Aged; AMP-Activated Protein Kinases; Colon; Diabetes Mellitus, Type 2; Enteroendocrine Cells; Equilibrative Nucleoside Transport Proteins; Female; Humans; Hypoglycemic Agents; Ileum; Intestinal Mucosa; Male; Metformin; Middle Aged; Peptide YY; Serotonin Plasma Membrane Transport Proteins; Weight Loss

Bariatric surgery is associated with significant and sustained weight loss and improved metabolic outcomes. It is unclear if weight loss alone is the main mechanism of improved metabolic health. The purpose of this trial was to compare indices of appetite regulation, insulin sensitivity and energy intake (EI) between participants achieving 10 kg of weight loss via Roux-en-Y Gastric Bypass (RYGB) or dietary restriction (DIET); intake of a very low calorie liquid diet (800 kcal/d; 40% protein, 40% fat, 20% carbohydrate that matched the post-RYGB dietary protocol). Adults qualifying for bariatric surgery were studied before and after 10 kg of weight loss (RYGB [n = 6]) or DIET [n = 17]). Appetite (hunger, satiety, and prospective food consumption [PFC]), appetite-related hormones, and metabolites (ghrelin, PYY, GLP-1, insulin, glucose, free fatty acids [FFA], and triglycerides [TG]) were measured in the fasting state and every 30 min for 180 min following breakfast. Participants were provided lunch to evaluate acute ad libitum EI, which was similarly reduced in both groups from pre to post weight loss. Fasting ghrelin was reduced to a greater extent following RYGB compared to DIET (P = 0.04). Area under the curve (AUC) for ghrelin (P = 0.01), hunger (P < 0.01) and PFC (P < 0.01) increased after DIET compared to RYGB, following 10 kg weight loss. Satiety AUC increased after RYGB and decreased after DIET (P < 0.01). Glucose and insulin (fasting and AUC) decreased in both groups. FFA increased in both groups, with a greater increase in AUC seen after RYGB versus DIET (P = 0.02). In summary, appetite-related indices were altered in a manner that, if maintained, may promote a sustained reduction in energy intake with RYGB compared to DIET. Future work with a larger sample size and longer follow-up will be important to confirm and extend these findings.

Topics: Adult; Appetite; Appetite Regulation; Blood Glucose; Body Mass Index; Diet, Reducing; Energy Intake; Female; Gastric Bypass; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Obesity; Peptide YY; Postprandial Period; Satiation; Weight Loss

The impact of lifestyle-induced weight loss (WL) on appetite in patients with obesity remains controversial. This study aimed to assess the short- and long-term impact of WL achieved by diet and exercise on appetite in patients with obesity. Thirty-five (22 females) adults with severe obesity (body mass index: 42.5 ± 5.0 kg/m

Topics: Adult; Anaerobic Threshold; Appetite Regulation; Body Mass Index; Diet, Reducing; Exercise; Female; Glucagon-Like Peptide 1; Humans; Hunger; Life Style; Male; Middle Aged; Obesity; Obesity, Morbid; Patient Care Team; Peptide YY; Weight Loss

Topics: Adiponectin; Adult; alpha-MSH; Energy Metabolism; Female; Gastric Bypass; Humans; Leptin; Male; Middle Aged; Obesity; Peptide YY; Prospective Studies; Treatment Outcome; Weight Loss

Gastric bypass surgery leads to profound changes in the secretion of gut hormones with effects on metabolism, appetite, and food intake. Here, we discuss their contributions to the improvement in glucose tolerance and the weight loss that results from the operations. We find that the improved glucose tolerance is due the following events: a negative energy balance and resulting weight loss, which improve first hepatic and later peripheral insulin sensitivity, in combination with increased postprandial insulin secretion elicited particularly by exaggerated glucagon-like peptide-1 responses. The weight loss is due to loss of appetite resulting in reduced energy intake, and we find it probable that this process is driven by exaggerated secretion of appetite-regulating gut hormones including, but probably not limited to, glucagon-like peptide-1 and peptide-YY. The increased secretion is due to an accelerated exposure to and absorption of nutrients in the small intestine. This places the weight loss and the gut hormones in key positions with respect to the metabolic improvements after bypass surgery.

Topics: Appetite; Bariatric Surgery; Diabetes Mellitus, Type 2; Dietary Carbohydrates; Dietary Proteins; Digestion; Eating; Gastric Bypass; Gastrointestinal Hormones; Glucagon-Like Peptide 1; Humans; Insulin Resistance; Intestinal Absorption; Nutrients; Obesity, Morbid; Peptide YY; Weight Loss

Diet-induced weight loss (WL) leads to a compensatory increase in appetite and changes in the plasma concentration of appetite-regulating hormones are likely to play a role. Whether these changes are transient or sustained remains unclear. This study aimed to assess if changes in subjective and objective appetite markers observed with WL are sustained after 1 year (1Y).. At Wk13, 16% WL (-18 ± 1 kg, P < 0.001) was associated with a significant increase in fasting and postprandial hunger ratings (P < 0.01 and P < 0.05, respectively), and postprandial fullness (P < 0.01) combined with a reduction in PFC (P < 0.001). These were accompanied by a significant rise in basal and postprandial AG concentrations (P < 0.001, for both), a reduction in postprandial CCK (P < 0.01) and in basal and postprandial insulin (P < 0.001). At 1Y follow-up, with sustained WL (15%; -16 ± 1 kg, P < 0.001), fasting hunger and postprandial fullness ratings remained increased (P < 0.05 for both), and postprandial PFC reduced (P < 0.001). Basal and postprandial AG remained elevated and insulin reduced (P < 0.001, for all), while postprandial CCK was increased (P < 0.01) and PYY decreased (P < 0.001).. With a 15% sustained WL at 1Y, the drive to eat in the fasting state is increased, but this may be balanced out by raised postprandial feelings of fullness. To assist with WL maintenance, new strategies are required to manage increased hunger and drive to eat.

Topics: Adult; Appetite; Body Weight; Diet; Female; Ghrelin; Humans; Longitudinal Studies; Male; Middle Aged; Peptide YY; Postprandial Period; Weight Gain; Weight Loss

Diet-induced weight loss (WL) leads to increased hunger and reduced fullness feelings, increased ghrelin and reduced satiety peptides concentration (glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK) and peptide YY (PYY)). Ketogenic diets seem to minimise or supress some of these responses. The aim of this study was to determine the timeline over which changes in appetite occur during progressive WL with a ketogenic very-low-energy diet (VLED).. Thirty-one sedentary adults (18 men), with obesity (body mass index: 37±4.5 kg m. A significant increase in fasting hunger was observed by day 3 (2±1% WL), (P<0.01), 5% WL (12±8 days) (P<0.05) and wk 13 (17±2% WL) (P<0.05). Increased desire to eat was observed by day 3 (P<0.01) and 5% WL (P<0.05). Postprandial prospective food consumption was significantly reduced at wk 9 (16±2% WL) (P<0.01). Basal total PYY was significantly reduced at 10% WL (32±8 days) (P<0.05). Postprandial active GLP-1 was increased at 5% WL (P<0.01) and CCK reduced at 5 and 10% WL (P<0.01, for both) and wk 9 (P<0.001). Basal and postprandial AG were significantly increased at wk 13 (P<0.001, both).. WL with a ketogenic VLED transiently increases the drive to eat up to 3 weeks (5% WL). After that, and while participants are ketotic, a 10-17% WL is not associated with increased appetite. However, hunger feelings and AG concentrations increase significantly from baseline, once refeeding occurs.

Topics: Adult; Appetite Regulation; Area Under Curve; Body Mass Index; Cholecystokinin; Diet, Ketogenic; Fasting; Female; Ghrelin; Glucagon-Like Peptide 1; Humans; Hunger; Longitudinal Studies; Male; Middle Aged; Norway; Obesity; Peptide YY; Postprandial Period; Satiety Response; Time Factors; Weight Loss

Topics: Humans; Pancreatic Polypeptide; Peptide YY; Proteolysis; Weight Loss

BACKGROUNDː The mechanisms underlying the metabolic effect of surgical treatment for morbid obesity are still unclear. Furthermore, the hormonal and metabolic response to the promising and less-invasive version of Roux-en-Y gastric bypass (RYGB), i.e. mini gastric bypass (MGB), is poorly known. The aim of this study was to evaluate pre- and postprandial changes in peptide YY (PYY) and metabolic parameters in obese patients without diabetes and cardiovascular complications treated by both versions of gastric bypass. METHODSː Venous blood for PYY and other assays was collected three months before and six months after bariatric operation (MGB and RYGB), in the fasting state and two hours after the consumption of a standard 300-kcal mixed meal (Nutridrink Standard, Nutricia Advanced Medical Nutrition, part of the Danone company, Schiphol, The Netherlands). RESULTSː In the MGB group, elevated concentrations of the PYY has been detected both fasting and postprandially. The effect of the MGB on the PYY levels did not differ from the RYGB group outcomes. CONCLUSIONSː The results of our study suggest similar endocrine and metabolic effects of MGB and RYGB procedures. Long-term efficacy and metabolic benefits of MGB require further research.

Topics: Adult; Biomarkers; Body Mass Index; Fasting; Female; Gastric Bypass; Humans; Laparoscopy; Male; Middle Aged; Obesity, Morbid; Peptide YY; Postoperative Care; Predictive Value of Tests; Preoperative Care; Prospective Studies; Sensitivity and Specificity; Treatment Outcome; Weight Loss

Apolipoprotein A-IV (ApoA-IV) has been shown to be involved in obesity and diabetes pathogenesis in animal studies, but its role in humans is uncertain.. The objective of this study was to determine the relation of ApoA-IV with changes in glucose metabolism and weight after bariatric surgery.. University Hospital.. The patients (n = 49) included lean controls (n = 8) and patients before and after a mean of 7 months after laparoscopic adjustable gastric banding (LAGB, n = 12), laparoscopic Roux-en-Y gastric bypass (RYGB, n = 22), or laparoscopic sleeve gastrectomy (SG, n = 11). ApoA-IV and other hormone assays were performed in the fasting and the postprandial state. Pearson's correlation analyses controlled for baseline BMI and percent excess weight loss (EWL) were used to determine relationships between ApoA-IV levels and insulin resistance (HOMA-IR).. With all bariatric procedures combined, the change in ApoA-IV [533 versus 518 microg/L, P = .813] or ApoA-IV area under the curve (AUC - 1072 versus 1042, P = .939) was not significant. None of the surgeries individually affected levels of fasting or ApoA-IV AUC. Bariatric surgery resulted in a decrease in HOMA-IR (5.3 versus 2.0, P<.001). In the RYGB group, higher baseline ApoA-IV levels correlated with decrease in HOMA-IR [r = -.6, P = .008]. This relationship was independent of EWL and was not observed in the LAGB or SG group. There was no association of ApoA-IV levels with EWL, insulin secretion, Peptide-YY, or leptin levels.. Preoperative ApoA-IV levels, rather than changes in levels, positively correlate with improvements in insulin sensitivity independent of weight loss after RYGB.

Topics: Adult; Apolipoproteins A; Blood Glucose; Body Mass Index; Case-Control Studies; Diabetes Mellitus, Type 2; Fasting; Female; Gastrectomy; Gastric Bypass; Gastroplasty; Humans; Insulin Resistance; Laparoscopy; Male; Obesity; Peptide YY; Postoperative Care; Postprandial Period; Preoperative Care; Weight Loss

To introduce a lower-risk novel surgical procedure to achieve diabetes reversal along with associated hormonal changes.. Diabetic rats were randomly assigned to jejunum-ileum circuit (JIC), sham-JIC, ileal interposition (IT), and sham-IT groups. The JIC group included two subgroups: short (JIC-S) and long (JIC-L), based on the length between anastomosis and Treitz ligament (LAT ). The body weight, food intake, blood glucose, glucose and insulin tolerance, and gut hormones were measured. The liver gene expression of glucose transporter 2 (GLUT2) and protein expression of glucose-6-phosphatase (G6P) and phosphoenolpyruvate carboxykinase (PKC) were also measured. Following a dye infusion, nutrient delivery was measured at termination day.. Compared to sham-JIC group, JIC-S group did not reduce body weight or food intake but significantly improved glucose tolerance and insulin resistance. With fast chyme transit, JIC-S not only promoted the secretion of insulin, glucagon-like peptide 1, and peptide YY and decreased leptin, but also upregulated hepatic GLUT2 and downregulated hepatic G6P and PKC. JIC-L group, however, failed to achieve remission of diabetes.. JIC-S relieves diabetes independent of weight loss, as it promotes the secretion of anti-diabetic hormones and inhibits hepatic glucose production. The prolonging of LAT , however, diminishes the hypoglycemic effect.

Topics: Animals; Biomarkers; Blood Glucose; Diabetes Mellitus, Experimental; Gastrointestinal Hormones; Glucagon-Like Peptide 1; Glucose; Glucose Intolerance; Glucose-6-Phosphatase; Ileum; Jejunum; Male; Peptide YY; Rats; Rats, Sprague-Dawley; Weight Loss

To investigate the anorectic effect of L-arginine (L-Arg) in rodents.. We investigated the effects of L-Arg on food intake, and the role of the anorectic gut hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), the G-protein-coupled receptor family C group 6 member A (GPRC6A) and the vagus nerve in mediating these effects in rodents.. Oral gavage of L-Arg reduced food intake in rodents, and chronically reduced cumulative food intake in diet-induced obese mice. Lack of the GPRC6A in mice and subdiaphragmatic vagal deafferentation in rats did not influence these anorectic effects. L-Arg stimulated GLP-1 and PYY release in vitro and in vivo. Pharmacological blockade of GLP-1 and PYY receptors did not influence the anorectic effect of L-Arg. L-Arg-mediated PYY release modulated net ion transport across the gut mucosa. Intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administration of L-Arg suppressed food intake in rats.. L-Arg reduced food intake and stimulated gut hormone release in rodents. The anorectic effect of L-Arg is unlikely to be mediated by GLP-1 and PYY, does not require GPRC6A signalling and is not mediated via the vagus. I.c.v. and i.p. administration of L-Arg suppressed food intake in rats, suggesting that L-Arg may act on the brain to influence food intake. Further work is required to determine the mechanisms by which L-Arg suppresses food intake and its utility in the treatment of obesity.

Topics: Animals; Appetite Depressants; Arginine; Cells, Cultured; Dietary Supplements; Energy Intake; Energy Metabolism; Gastrointestinal Agents; Glucagon-Like Peptide 1; In Vitro Techniques; Injections, Intraperitoneal; Injections, Intraventricular; Intestinal Mucosa; Male; Mice, Inbred C57BL; Mice, Knockout; Obesity; Peptide YY; Random Allocation; Rats, Wistar; Receptors, G-Protein-Coupled; Weight Loss

The hormones glucagon-like peptide 1 (GLP-1), peptide YY3-36 (PYY3-36), ghrelin, glucose-dependent insulinotropic polypeptide (GIP) and glucagon have all been implicated in the pathogenesis of obesity. However, it is unknown whether they exhibit adaptive changes with respect to postprandial secretion to a sustained weight loss.. The study was designed as a longitudinal prospective intervention study with data obtained at baseline, after 8 weeks of weight loss and 1 year after weight loss.. Twenty healthy obese individuals obtained a 13% weight loss by adhering to an 8-week very low-calorie diet (800kcal/day). After weight loss, participants entered a 52-week weight maintenance protocol. Plasma levels of GLP-1, PYY3-36, ghrelin, GIP and glucagon during a 600-kcal meal were measured before weight loss, after weight loss and after 1 year of weight maintenance. Area under the curve (AUC) was calculated as total AUC (tAUC) and incremental AUC (iAUC).. Weight loss was successfully maintained for 52 weeks. iAUC for GLP-1 increased by 44% after weight loss (P<0.04) and increased to 72% at week 52 (P=0.0001). iAUC for PYY3-36 increased by 74% after weight loss (P<0.0001) and by 36% at week 52 (P=0.02). tAUC for ghrelin increased by 23% after weight loss (P<0.0001), but at week 52, the increase was reduced to 16% compared with before weight loss (P=0.005). iAUC for GIP increased by 36% after weight loss (P=0.001), but returned to before weight loss levels at week 52. Glucagon levels were unaffected by weight loss.. Meal responses of GLP-1 and PYY3-36 remained increased 1 year after weight maintenance, whereas ghrelin and GIP reverted toward before-weight loss values. Thus, an increase in appetite inhibitory mechanisms and a partly decrease in appetite-stimulating mechanisms appear to contribute to successful long-term weight loss maintenance.

Topics: Adaptation, Physiological; Adolescent; Adult; Aged; Female; Glucagon-Like Peptide 1; Humans; Longitudinal Studies; Male; Middle Aged; Peptide Fragments; Peptide YY; Postprandial Period; Weight Loss; Young Adult

Body weight varies depending on the prevailing direction of environmental pressures; however, physiological factors also play a significant role in the control of body weight. The aim of the present study was to assess the impact of Roux-en-Y gastric bypass (RYGB) on hormones and peptides involved in the control of energy balance and their possible implications in appetite/satiety.. The sample included 39 individuals with extreme obesity (37 women and two men) who underwent RYGB. Anthropometric and biochemical markers were collected before surgery and 6 months after RYGB.. The BMI decreased from 44.3±6.4 to 31.7±5.7 kg/m (P<0.001) at the sixth month. Percentage of excess weight lost was 63.2±25.0%. Leptin and glucose levels decreased significantly 6 months after RYGB (P<0.001). Interestingly, a significant correlation was confirmed between the anorexigenic gut hormone peptide YY (PYY) and the central anorexigenic mediator α-melanocyte-stimulating hormone after 6 months of RYGB (r=0.35, P=0.004). In contrast, PYY concentrations were correlated negatively with BMI (r=-0.34, P=0.002).. In the present investigation, it was found that there is a relationship between α-melanocyte-stimulating hormone and PYY concentrations, and it supports the role of the PYY to POMC signal in appetite regulation after RYGB.

Topics: Adult; alpha-MSH; Appetite Regulation; Blood Glucose; Body Mass Index; Energy Metabolism; Gastric Bypass; Gastric Mucosa; Humans; Leptin; Male; Middle Aged; Obesity, Morbid; Peptide Hormones; Peptide YY; Stomach; Time Factors; Treatment Outcome; Weight Loss; Young Adult

Gastric bypass surgery (GBP) leads to sustained weight loss and significant improvement in type 2 diabetes (T2DM). Bile acids (BAs), signaling molecules which influence glucose metabolism, are a potential mediator for the improvement in T2DM after GBP. This study sought to investigate the effect of GBP on BA levels and composition in individuals with T2DM.. Plasma BA levels and composition and fibroblast growth factor (FGF)-19 levels were measured during fasting and in response to an oral glucose load before and at 1 month and 2 years post GBP in 13 severely obese women with T2DM.. A striking temporal change in BA levels and composition was observed after GBP. During the fasted state, BA concentrations were generally reduced at 1 month, but increased 2 years post GBP. Postprandial BA levels were unchanged 1 month post GBP, but an exaggerated postprandial peak was observed 2 years after the surgery. A significant increase in the 12α-hydroxylated/non12α-hydroxylated BA ratio during fasting and postprandially at 2 years, but not 1 month, post GBP was observed. Significant correlations between BAs vs FGF-19, body weight, the incretin effect and peptide YY (PYY) were also found.. This study provides evidence that GBP temporally modifies the concentration and composition of circulating BAs in individuals with T2DM, and suggests that BAs may be linked to the improvement in T2DM after GBP.

Topics: Adult; Bile Acids and Salts; Diabetes Mellitus, Type 2; Fasting; Female; Gastric Bypass; Humans; Hydroxylation; Middle Aged; Obesity, Morbid; Peptide YY; Postoperative Period; Postprandial Period; Prospective Studies; Time Factors; Treatment Outcome; Weight Loss

Understanding the mechanisms that drive weight loss in a lean population may elucidate systems that regulate normal energy homeostasis. This prospective study of British military volunteers investigated the effects of a 6-month deployment to Afghanistan on energy balance and circulating concentrations of specific appetite-regulating hormones.. Measurements were obtained twice in the UK (during the Pre-deployment period) and once in Afghanistan, at Mid-deployment. Body mass, body composition, food intake, and appetite-regulatory hormones (leptin, active and total ghrelin, PYY, PP, GLP-1) were measured.. Repeated measures analysis of 105 volunteers showed body mass decreased by 4.9% ± 3.7% (P < 0.0001) during the first half of the deployment. Leptin concentrations were significantly correlated with percentage body fat at each time point. The reduction in percentage body fat between Pre-deployment and Mid-deployment was 8.6%, with a corresponding 48% decrease in mean circulating leptin. Pre-deployment leptin and total and active ghrelin levels correlated with subsequent change in body mass; however. no changes were observed in the anorectic gut hormones GLP-1, PP, or PYY.. These data suggest that changes in appetite-regulating hormones in front line military personnel occur in response to, but do not drive, reductions in body mass.

Topics: Adult; Afghan Campaign 2001-; Afghanistan; Body Composition; Eating; Energy Metabolism; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Leptin; Male; Middle Aged; Military Personnel; Peptide YY; Prospective Studies; Weight Loss; Young Adult

The majority of weight loss studies fail to standardize conditions such as diet and exercise via a weight maintenance period prior to commencement of the trial. This study aimed to determine whether a weight stabilization period is necessary to establish stable baseline hormone concentrations. Fifty-one obese male participants with a body mass index of 30-40 kg m(-2) and aged 25-54 years underwent 4 weeks on an energy balance diet that was designed to achieve weight stability. Blood samples were collected in the fasting state at commencement and completion of the 4-week period, and circulating concentrations of 18 commonly measured hormones were determined. During the 4-week weight maintenance period, participants achieved weight stability within -1.5 ± 0.2 kg (-1.4 ± 0.2%) of their initial body weight. Significant reductions in serum insulin (by 18 ± 6.5%) and leptin (by 21 ± 6.0%) levels occurred, but no significant changes were observed for gut-derived appetite-regulating hormones (ghrelin and peptide YY), nor thyroid, adrenal, gonadal or somatotropic hormones. There were no significant correlations between the change in body weight and the change in circulating concentrations of insulin or leptin over the 4-week period, indicating that the observed changes were not due to weight loss, albeit significant negative correlations were observed between the changes in body weight and plasma ghrelin and peptide YY levels. This study demonstrates the need for baseline weight maintenance periods to stabilize serum levels of insulin and leptin in studies specifically investigating effects on these parameters in the obese. However, this does not apply to circulating levels of gut-derived appetite-regulating hormones (ghrelin and peptide YY), nor thyroid, adrenal, gonadal or somatotropic hormones.

Topics: Adult; Clinical Trials as Topic; Diet; Energy Metabolism; Ghrelin; Hormones; Humans; Insulin; Leptin; Male; Middle Aged; Obesity; Peptide YY; Research Design; Weight Loss

Activation of TGR5 via bile acids or bile acid analogs leads to the release of glucagon-like peptide-1 (GLP-1) from intestine, increases energy expenditure in brown adipose tissue, and increases gallbladder filling with bile. Here, we present compound 18, a non-bile acid agonist of TGR5 that demonstrates robust GLP-1 secretion in a mouse enteroendocrine cell line yet weak GLP-1 secretion in a human enteroendocrine cell line. Acute administration of compound 18 to mice increased GLP-1 and peptide YY (PYY) secretion, leading to a lowering of the glucose excursion in an oral glucose tolerance test (OGTT), while chronic administration led to weight loss. In addition, compound 18 showed a dose-dependent increase in gallbladder filling. Lastly, compound 18 failed to show similar pharmacological effects on GLP-1, PYY, and gallbladder filling in Tgr5 knockout mice. Together, these results demonstrate that compound 18 is a mouse-selective TGR5 agonist that induces GLP-1 and PYY secretion, and lowers the glucose excursion in an OGTT, but only at doses that simultaneously induce gallbladder filling. Overall, these data highlight the benefits and potential risks of using TGR5 agonists to treat diabetes and metabolic diseases.

Topics: Animals; Drug Evaluation, Preclinical; Gallbladder; Gene Expression Regulation; Glucagon-Like Peptide 1; Glucose Tolerance Test; HEK293 Cells; Humans; Hypoglycemic Agents; Male; Mice, Inbred C57BL; Mice, Knockout; Peptide YY; Receptors, G-Protein-Coupled; Small Molecule Libraries; Weight Loss

Gastrointestinal hormones are critically involved in the regulation of food intake and body weight. Previous studies support an interplay between gastrointestinal hormones and the serotonergic system. This study explored intestinal neuroendocrine expression patterns in humans with obesity versus nonobese humans.. Jejunum samples were collected from 164 humans with obesity (120 women; BMI (mean ± SD): 43.5 ± 6.6 kg/m(2) ) while they underwent Roux-en-Y gastric bypass surgery and from 18 nonobese humans (7 women; BMI: 23.5 ± 3.0 kg/m(2) ) undergoing distinct intestinal surgeries. mRNA expression of cholecystokinin (CCK), peptide YY3-36 (PYY), nesfatin1, ghrelin, ghrelin O-acyltransferase (GOAT), leptin, leptin receptor (leptinR), glucagon-like-peptide 1 receptor (GLP1R), serotonin transporter (SERT), tryptophan hydroxylase 1 (TPH1), and serotonin receptor 3A (5HT3A R) was determined with qRT-PCR. Ghrelin and GOAT protein expression was quantified using immunohistological stainings. Statistical analyses were performed with SPSS.. Jejunum samples from humans with obesity showed a higher expression of GOAT (mRNA and protein), TPH1, and SERT mRNA compared with the nonobese humans (all P < 0.05). Positive correlations were observed between TPH1, CCK, PYY, and nesfatin1 in nonobese and GOAT, ghrelin, TPH1, SERT, CCK, and PYY in humans with obesity (all P < 0.01).. Our top-down approach substantiates the dysregulation of jejunal neuroendocrine hormones in obesity.

Topics: Acyltransferases; Adult; Aged; Aged, 80 and over; Case-Control Studies; Cholecystokinin; Female; Gastric Bypass; Gastrointestinal Hormones; Gene Expression Regulation; Ghrelin; Humans; Jejunum; Leptin; Middle Aged; Neuroendocrine Cells; Obesity, Morbid; Peptide Fragments; Peptide YY; Weight Loss; Young Adult

Factors underlying variable weight loss (WL) after Roux-en-Y gastric bypass (RYGB) are poorly understood.. Our objective was to gain insight on the role of gastrointestinal hormones on poor WL maintenance (P-WLM) following RYGB.. First, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and ghrelin responses to a standardized mixed liquid meal (SMLM) were compared between subjects with good WL (G-WL, n = 32) or P-WLM (n = 22). Second, we evaluated food intake (FI) following blockade of gut hormonal secretion in G-WL (n = 23) or P-WLM (n = 19) subjects. Finally, the impact of dietary-induced WL on the hormonal response in subjects with P-WLM (n = 14) was assessed.. This study was undertaken in a tertiary hospital.. In studies 1 and 3, the outcomes measures were the areas under the curve of gut hormones following a SMLM; in study 2, FI following subcutaneous injection of saline or octreotide were evaluated.. P-WLM associated a blunted GLP-1 (P = .044) and PYY (P = .001) responses and lesser suppression of ghrelin (P = .032) following the SMLM challenge. On saline day, FI in the G-WL (393 ± 143 kcal) group was less than in the P-WLM (519 ± 143 Kcal; P = .014) group. Octreotide injection resulted in enlarged FI in both groups (G-WL: 579 ± 248 kcal, P = .014; P-WLM: 798 ± 284 Kcal, P = .036), but the difference in FI between groups remained (P < .001). In subjects with P-WLM, dietary-induced WL resulted in larger ghrelin suppression (P = .046), but no change in the GLP-1 or PYY responses.. Our data show gastrointestinal hormones play a role in the control of FI following RYGB, but do not support that changes in GLP-1, PYY, or ghrelin play a major role as determinants of P-WLM after this type of surgery.

Topics: Adult; Case-Control Studies; Cohort Studies; Diet; Diet, Reducing; Eating; Female; Gastric Bypass; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Obesity, Morbid; Octreotide; Peptide YY; Treatment Outcome; Weight Loss

The significant weight loss observed with combination naltrexone-sustained release (SR) 32 mg and bupropion SR 360 mg (NB32) therapy is thought to be due, in part, to bupropion stimulation of hypothalamic pro-opiomelanocortin (POMC) neurons, and naltrexone blockade of opioid receptor-mediated POMC autoinhibition, but the neurobiological mechanisms are not fully understood. We assessed changes in brain reactivity to food cues before and after NB32 treatment.. Forty women (31.1±8.1 years; body mass index: 32.5±3.9) received 4 weeks of NB32 or placebo, and were instructed to maintain their dietary and exercise habits. Functional magnetic resonance imaging responses (analyzed using SPM2 and clusters (>100 pixels)) to a 5-min food video (preparation of the subject's favorite food) and a 5-min neutral video (manipulation of neutral objects) under conditions of mild food deprivation (∼14 h) were assessed before and after treatment.. The food cues video induced positive brain activation in visual and prefrontal cortices, insula and subcortical brain regions. The group-by-treatment interaction on regional brain activation was significant and showed that whereas NB32 attenuated the activation in the hypothalamus in response to food cues (P<0.01), it enhanced activation in regions involved in inhibitory control (anterior cingulate), internal awareness (superior frontal, insula, superior parietal) and memory (hippocampal) regions (whole-brain analysis; P<0.05).. Blunting the hypothalamic reactivity to food cues while enhancing the activation of regions involved with self-control and internal awareness by NB32 might underlie its therapeutic benefits in obesity.

Topics: Adolescent; Adult; Appetite; Bupropion; Cues; Diet; Dopamine Uptake Inhibitors; Drug Therapy, Combination; Female; Ghrelin; Humans; Hypothalamus; Leptin; Magnetic Resonance Imaging; Meals; Naltrexone; Obesity; Peptide YY; Treatment Outcome; Weight Loss

Laparoscopic Roux-en-Y gastric bypass (LRYGBP) reduces appetite and induces significant and sustainable weight loss. Circulating gut hormones changes engendered by LRYGBP are implicated in mediating these beneficial effects. Laparoscopic sleeve gastrectomy (LSG) is advocated as an alternative to LRYGBP, with comparable short-term weight loss and metabolic outcomes. LRYGBP and LSG are anatomically distinct procedures causing differential entero-endocrine cell nutrient exposure and thus potentially different gut hormone changes. Studies reporting the comparative effects of LRYGBP and LSG on appetite and circulating gut hormones are controversial, with no data to date on the effects of LSG on circulating peptide YY3-36 (PYY3-36) levels, the specific PYY anorectic isoform. In this study, we prospectively investigated appetite and gut hormone changes in response to LRYGBP and LSG in adiposity-matched non-diabetic patients. Anthropometric indices, leptin, fasted and nutrient-stimulated acyl-ghrelin, active glucagon-like peptide-1 (GLP-1), PYY3-36 levels and appetite were determined pre-operatively and at 6 and 12 weeks post-operatively in obese, non-diabetic females, with ten undergoing LRYGBP and eight adiposity-matched females undergoing LSG. LRYGBP and LSG comparably reduced adiposity. LSG decreased fasting and post-prandial plasma acyl-ghrelin compared to pre-surgery and to LRYGBP. Nutrient-stimulated PYY3-36 and active GLP-1 concentrations increased post-operatively in both groups. However, LRYGBP induced greater, more sustained PYY3-36 and active GLP-1 increments compared to LSG. LRYGBP suppressed fasting hunger compared to LSG. A similar increase in post-prandial fullness was observed post-surgery following both procedures. LRYGBP and LSG produced comparable enhanced satiety and weight loss. However, LSG and LRYGBP differentially altered gut hormone profiles.

Topics: Adolescent; Adult; Appetite; Body Mass Index; Female; Gastrectomy; Gastric Bypass; Ghrelin; Glucagon-Like Peptide 1; Humans; Laparoscopy; Middle Aged; Obesity, Morbid; Peptide Fragments; Peptide YY; Prospective Studies; Treatment Outcome; Weight Loss

Enhanced stimulation of the lower gut is hypothesized to play a key role in the weight loss and resolution of diabetes following bariatric surgeries. Ileal transposition (IT) permits study of the effects of direct lower gut stimulation on body weight, glucose homeostasis and other metabolic adaptations without the confounds of gastric restriction or foregut exclusion. However, the underlying mechanisms and the length of the ileum sufficient to produce metabolic benefits following IT surgery remain largely unknown.. To determine the effects of transposing varying lengths of the ileum to upper jejunum on food intake, body weight, glucose tolerance and lower gut hormones, and the expression of key markers of glucose and lipid metabolism in skeletal muscle and adipose tissue in rats.. Adult male Sprague-Dawley rats (n=9/group) were subjected to IT surgery with translocation of 5, 10 or 20 cm of the ileal segment to proximal jejunum or sham manipulations. Daily food intake and body weight were recorded, and an intraperitoneal glucose tolerance test was performed. Blood samples were assayed for hormones and tissue samples for mRNA (RT-qPCR) and/or protein abundance (immunoblotting) of regulatory metabolic markers.. We demonstrate that IT surgery exerts ileal length-dependent effects on multiple parameters including: (1) decreased food intake and weight gain, (2) improved glucose tolerance, (3) increased tissue expression and plasma concentrations of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), and decreased leptin concentrations and (4) upregulation of key markers of glucose metabolism (glucose transporter-4 (GLUT-4), insulin receptor substrate 1 (IRS-1), adenosine monophosphate-activated protein kinase (AMPK), hexokinase (HK) and phosphofructokinase (PFK)) together with a downregulation of lipogenic markers (fatty acid synthase (FAS)) in muscle and adipose tissue.. Together, our data demonstrate that the reduction in food intake and weight gain, increase in lower gut hormones, glycemic improvements and associated changes in tissue metabolic markers following IT surgery are dependent on the length of the transposed ileum.

Topics: AMP-Activated Protein Kinases; Animals; Biomarkers; Blood Glucose; Eating; Gastrectomy; Gastrointestinal Hormones; Glucagon-Like Peptide 1; Glucose Tolerance Test; Glucose Transporter Type 4; Homeostasis; Ileum; Insulin Receptor Substrate Proteins; Intestinal Mucosa; Leptin; Male; Muscle, Skeletal; Peptide YY; Rats; Rats, Sprague-Dawley; Weight Loss

The mechanisms of weight loss after gastric bypass, including the role of gastric hormones, are still not completely understood. While postprandial releases of peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) increase post-surgery and ghrelin usually is reduced, their relationship to the magnitude of the weight loss is still obscure. We explored if differing weight loss after Roux Y gastric bypass (RYGB) in morbidly obese were associated with differing postprandial hormonal release.. We compared patients with large (> 40%) or moderate (< 25%) weight loss three years following RYGP surgery, and an obese control group scheduled for RYGB (six in each group). A 300 kcal mixed meal test was given with blood sampling before and thereafter at 30-min intervals in 180 min. Peak and incremental area under the curve (iAUC) were calculated to characterize postprandial responses.. Early postprandial GLP-1 response were significantly higher in the RYGB groups than in the controls, and highest in those with largest weight loss. Postprandial PYY response were also greater for the two RYGB groups vs. controls, but interestingly the controls had higher baseline values. Ghrelin, from similar baseline, was only suppressed in those with the largest weight loss, with close to no reduction in those with modest weight loss or controls.. These results support the hypothesis that the magnitude of weight loss after RYGB surgery might be associated with differing patterns of postprandial responses in GLP-1 and ghrelin, but not PYY. Larger studies are warranted.

Topics: Adult; Anastomosis, Roux-en-Y; Area Under Curve; Female; Gastric Bypass; Gastric Mucosa; Ghrelin; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Obesity, Morbid; Peptide YY; Postprandial Period; Stomach; Weight Loss

Weight loss is the result of a sustained negative energy balance, which is typically achieved by decreasing food intake and/or increasing physical activity. Current evidence suggests that acute energy deficits of ~4820 kJ elicit contrasting homeostatic responses when induced by exercise and food restriction but the response to government-recommended energy deficits is unknown. Twelve healthy men (mean(SD): age 24(5) years, body mass index 23.8(2.7) kg⋅m(-2), maximum oxygen uptake 55.4(9.1) mL⋅kg(-1)⋅min(-1)) completed three 8 h trials (control (Con), exercise-induced energy deficit (Ex-Def) and food restriction (Food-Def)) separated by 1 week. Thirty minutes of cycling at 64.5(3.2)% of maximum oxygen uptake was performed in Ex-Def from 0 to 0.5 h, which induced an energy deficit of 1469(256) kJ. An equivalent energy deficit was induced in Food-Def (1478(275) kJ) by reducing the energy content of standardised test meals at 1 h and 4 h. Appetite ratings, acylated ghrelin and peptide YY3-36 concentrations were measured throughout each trial. An ad libitum meal was provided at 7 h. Appetite was higher in Food-Def than Ex-Def from 4 to 8 h (P = 0.033) and tended to be higher across the entire 8 h trial (P = 0.059). However, energy intake at the ad libitum meal did not differ between trials (P = 0.634; Con 4376 (1634); Food-Def 4481 (1846); Ex-Def 4217 (1850) kJ). Acylated ghrelin was not related to changes in appetite but plasma PYY3-36 concentrations were higher in Ex-Def than Food-Def (P < 0.05) and negatively correlated with changes in appetite across the entire 8 h trial (P = 0.037). An energy deficit of ~1475 kJ stimulated compensatory increases in appetite when induced via calorie restriction but not when achieved by an acute bout of exercise. Appetite responses were associated with changes in plasma PYY3-36 but not acylated ghrelin concentrations and did not influence subsequent energy intake.

Topics: Acylation; Adult; Appetite; Bicycling; Body Mass Index; Caloric Restriction; Energy Intake; Energy Metabolism; Exercise; Gastrointestinal Tract; Ghrelin; Healthy Volunteers; Humans; Male; Peptide Fragments; Peptide YY; Prospective Studies; Weight Loss; Young Adult

To identify factors contributing to the variation in weight loss after Roux-en-Y gastric bypass (RYGB).. Cross-sectional study of patients with good (excess body mass index lost (EBL) >60%) and poor weight loss response (EBL <50%) >12 months after RYGB and a lean control group matched for age and gender.. Sixteen patients with good weight loss response, 17 patients with poor weight loss response, and eight control subjects were included in the study. Participants underwent dual energy X-ray absorptiometry scan, indirect calorimetry and a 9 h multiple-meal test with measurements of glucose, insulin, total bile acids (TBA), glucagon-like peptide (GLP)-1, peptide YY3-36 (PYY), cholecystokinin (CCK), ghrelin, neurotensin and pancreatic polypeptide (PP) as well as assessment of early dumping and appetite.. Suppression of hunger was more pronounced in the good than the poor responders in response to the multiple-meal test (P=0.006). In addition, the good responders had a larger release of GLP-1 (P=0.009) and a greater suppression of ghrelin (P=0.037) during the test, whereas the postprandial secretion of CCK was highest in the poor responders (P=0.005). PYY, neurotensin, PP and TBA release did not differ between the RYGB-operated groups. Compared with control subjects, patients had exaggerated release of GLP-1 (P<0.001), PYY (P=0.008), CCK (P=0.010) and neurotensin (P<0.001). Early dumping was comparable in the good and poor responders, but more pronounced than in controlled subjects. Differences in resting energy expenditure between the three groups were entirely explained by differences in body composition.. Favorable meal-induced changes in hunger and gut hormone release in patients with good compared with poor weight loss response support the role of gut hormones in the weight loss after RYGB.

Topics: Absorptiometry, Photon; Appetite Regulation; Bile Acids and Salts; Blood Glucose; Body Mass Index; Cholecystokinin; Cross-Sectional Studies; Dumping Syndrome; Energy Metabolism; Female; Follow-Up Studies; Gastric Bypass; Ghrelin; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Neurotensin; Obesity, Morbid; Peptide YY; Treatment Outcome; Weight Loss

Weight regain after gastric bypass (GBP) can be associated with a gastrogastric fistula (GGF), in which a channel forms between the gastric pouch and gastric remnant, allowing nutrients to pass through the "old route" rather than bypassing the duodenum. To further understand the mechanisms by which GGF may lead to weight regain, we investigated gut hormone levels in GBP patients with a GGF, before and after repair.. Seven post-GBP subjects diagnosed with GGF were studied before and 4 months after GGF repair. Another cohort of 22 GBP control subjects without GGF complication were studied before and 1 year post-GBP. All subjects underwent a 50-g oral glucose tolerance test and blood was collected from 0-120 min for glucose, insulin, ghrelin, PYY3-36, GIP, and GLP-1 levels.. Four months after GGF repair subjects lost 6.0 ± 3.9 kg and had significantly increased postprandial PYY3-36 levels. After GGF repair, fasting and postprandial ghrelin levels decreased and were strongly correlated with weight loss. The insulin response to glucose also tended to be increased after GGF repair, however no concomitant increase in GLP-1 was observed. Compared to the post-GBP group, GLP-1 and PYY3-36 levels were significantly lower before GGF repair; however, after GGF repair, PYY3-36 levels were no longer lower than the post-GBP group.. These data utilize the GGF model to highlight the possible role of duodenal shunting as a mechanism of sustained weight loss after GBP, and lend support to the potential link between blunted satiety peptide release and weight regain.

Topics: Adult; Blood Glucose; Body Mass Index; Endoscopy, Gastrointestinal; Female; Gastric Bypass; Gastric Fistula; Gastrointestinal Hormones; Gastroscopy; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin; Laparoscopy; Male; Obesity, Morbid; Peptide Fragments; Peptide YY; Postoperative Complications; Postoperative Period; Preoperative Period; Suture Techniques; Time Factors; Treatment Outcome; United States; Weight Loss

Diet-induced weight loss is accompanied by compensatory changes, which increase appetite and encourage weight regain. There is some evidence that ketogenic diets suppress appetite. The objective is to examine the effect of ketosis on a number of circulating factors involved in appetite regulation, following diet-induced weight loss.. Of 50 non-diabetic overweight or obese subjects who began the study, 39 completed an 8-week ketogenic very-low-energy diet (VLED), followed by 2 weeks of reintroduction of foods. Following weight loss, circulating concentrations of glucose, insulin, non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHB), leptin, gastrointestinal hormones and subjective ratings of appetite were compared when subjects were ketotic, and after refeeding.. During the ketogenic VLED, subjects lost 13% of initial weight and fasting BHB increased from (mean±s.e.m.) 0.07±0.00 to 0.48±0.07 mmol/l (P<0.001). BHB fell to 0.19±0.03 mmol/l after 2 weeks of refeeding (P<0.001 compared with week 8). When participants were ketotic, the weight loss induced increase in ghrelin was suppressed. Glucose and NEFA were higher, and amylin, leptin and subjective ratings of appetite were lower at week 8 than after refeeding.. The circulating concentrations of several hormones and nutrients which influence appetite were altered after weight loss induced by a ketogenic diet, compared with after refeeding. The increase in circulating ghrelin and subjective appetite which accompany dietary weight reduction were mitigated when weight-reduced participants were ketotic.

Topics: 3-Hydroxybutyric Acid; Adult; Aged; Appetite Regulation; Body Mass Index; Caloric Restriction; Diet, Ketogenic; Fasting; Fatty Acids, Nonesterified; Female; Gastrointestinal Hormones; Ghrelin; Humans; Insulin; Islet Amyloid Polypeptide; Ketosis; Leptin; Male; Middle Aged; Obesity; Overweight; Peptide YY; Postmenopause; Weight Loss

Fibroblast growth factor (FGF)-19 and FGF-21 are novel metabolic regulators that improve insulin resistance and obesity in rodents. The aim of the study was to assess the effects of laparoscopic sleeve gastrectomy (LSG) on serum concentrations of FGF-19 and FGF-21 along with circulating bile acids and other relevant hormonal and biochemical parameters.. Seventeen females with obesity undergoing LSG and 15 lean healthy females were included into the study. Anthropometric and biochemical parameters, serum concentrations of FGF-19 and -21, insulin, adiponectin, leptin, C-reactive protein, resistin, amylin (total), ghrelin (active), glucagon-like peptide 1 (GLP-1, active), glucose-dependent insulinotropic peptide (GIP, total), peptide YY (PYY, total), pancreatic polypeptide (PP), and bile acids, and mRNA expression of selected adipokines and inflammatory markers in bioptic samples of subcutaneous fat were assessed at baseline and 6, 12, and 24 months after LSG.. LSG markedly decreased body weight, BMI, waist circumference, and insulin levels and improved systemic inflammation and lipid levels. FGF-19 concentrations increased and FGF-21 concentrations decreased after LSG along with increased adiponectin and decreased leptin, amylin, and ghrelin levels. GLP-1, GIP, PP, and circulating bile acids were not affected by LSG. PYY decreased significantly 24 months after surgery only. mRNA expression analysis in subcutaneous fat showed markedly reduced proinflammatory state.. Our results indicate that increased FGF-19 and decreased ghrelin concentrations could have partially contributed to the improvement of systemic inflammation and some metabolic parameters after LSG, while changes of FGF-21 are rather secondary because of weight loss.

Topics: Adiponectin; Adult; Bile Acids and Salts; Body Mass Index; C-Reactive Protein; Female; Fibroblast Growth Factors; Gastrectomy; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Islet Amyloid Polypeptide; Leptin; Middle Aged; Obesity, Morbid; Pancreatic Polypeptide; Peptide YY; Prospective Studies; Resistin; RNA, Messenger; Subcutaneous Fat; Waist Circumference; Weight Loss

Roux-en-Y gastric bypass (RYGB) is effective in controlling blood glucose in obese patients with type 2 diabetes (T2DM). The alterations of gut hormones involving in glucose metabolism may play an important role. Our aim was to explore the short-term effects of Billroth II gastrojejunostomy (a similar type of RYGB) on glucose metabolism and gut hormone modulations in nonobese patients with different levels of blood glucose tolerance.. Twenty one nonobese gastric cancer patients with different levels of blood glucose tolerance were submitted to Billroth II gastrojejunostomy. Among them, seven had T2DM, seven with impaired glucose tolerance (IGT) and the other seven had normal glucose tolerance (NGT). Body weight, glucose parameters, responses of plasma glucagon-like peptide-1 (GLP-1), peptide YY (PYY) and gastric inhibitory polypeptide (GIP) to 75 g glucose were measured at baseline and 3 months after surgery.. Similar weight losses were observed in all groups. Blood glucose was reduced in T2DM and IGT patients. Fasting and 30-min plasma glucose were increased significantly in NGT. GLP-1 showed insignificant alterations in all groups. PYY was evaluated in T2DM and IGT but remained unchanged in the NGT group. Decreased fasting and AUC GIP were observed in patients with T2DM; however, fasting and 30-min GIP were increased in NGT patients.. Billroth II gastrojejunostomy is effective in reducing blood glucose in nonobese patients with T2DM and IGT but could deteriorate early blood glucose in nonobese NGT in a 3-month time period. Variations of glucose and gut hormone changes in the three groups suggest a role of proximal intestine in the pathophysiology of T2DM.

Topics: Adult; Aged; Area Under Curve; Blood Glucose; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucose Intolerance; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Male; Middle Aged; Obesity; Peptide YY; Postoperative Period; Stomach Neoplasms; Weight Loss

Immune challenge of mice with Bacille Calmette-Guérin (BCG) has been reported to cause transient weight loss and a behavioural sickness response. Although BCG-induced depression involves the kynurenine pathway, weight loss occurs independently of this factor. Because neuropeptide Y (NPY) and peptide YY (PYY) are involved in the regulation of food intake, we hypothesized that they play a role in the BCG-induced weight loss.. Male wild-type, PYY knockout (PYY-/-), NPY knockout (NPY-/-) and NPY-/-;PYY-/- double knockout mice were injected with vehicle or BCG (approximately 10(8) colony-forming units per mouse), and their weight, locomotion, exploration and ingestion were recorded for 2 weeks post-treatment.. Deletion of PYY and NPY aggravated the BCG-induced loss of body weight, which was most pronounced in NPY-/-;PYY-/- mice (maximum loss: 15%). The weight loss in NPY-/-;PYY-/- mice did not normalize during the 2 week observation period. BCG suppressed the circadian pattern of locomotion, exploration and food intake. However, these changes took a different time course than the prolonged weight loss caused by BCG in NPY-/-;PYY-/- mice. The effect of BCG to increase circulating IL-6 (measured 16 days post-treatment) remained unaltered by knockout of PYY, NPY or NPY plus PYY.. These data show that NPY and PYY are both required to protect from the action of BCG-evoked immune challenge to cause prolonged weight loss and disturb energy balance. The findings attest to an important role of NPY and PYY in orchestrating homeostatic reactions to infection and immune stimulation.

Topics: Animals; BCG Vaccine; Behavior, Animal; Circadian Rhythm; Corticosterone; Eating; Energy Metabolism; Exploratory Behavior; Female; Interleukin-6; Male; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Motor Activity; Neuropeptide Y; Peptide YY; Time Factors; Weight Loss

Peptide YY (PYY) and ghrelin exhibit a reciprocal association and antagonistic physiological effects in the peripheral circulation. Research has yet to clarify the effect of weight loss on the 24h profile of PYY or its association to 24h ghrelin. We sought to determine if diet- and exercise-induced weight loss affects the 24h profile of PYY and its association with 24h ghrelin in normal weight, premenopausal women. Participants (n = 13) were assessed at baseline (BL) and after a 3-month diet and exercise intervention (post). Blood samples obtained q10 min for 24h were assayed for total PYY and total ghrelin q60 min from 0800 to 1000 h and 2000 to 0800 h and q20 min from 1000 to 2000 h. The ghrelin/PYY ratio was used as an index of hormonal exposure. Statistical analyses included paired t-tests and linear mixed effects modeling. Body weight (-1.85 ± 0.67 kg; p = 0.02), and body fat (-2.53 ± 0.83%; p = 0.01) decreased from BL to post. Ghrelin AUC (5252 ± 2177 pg/ml/24h; p=0.03), 24h mean (216 ± 90 pg/ml; p = 0.03) and peak (300 ± 134 pg/ml; p = 0.047) increased from BL to post. No change occurred in PYY AUC (88.2 ± 163.7 pg/ml; p = 0.60), 24h mean (4.8 ± 6.9 pg/ml; p = 0.50) or peak (3.6 ± 6.4 pg/ml; p = 0.58). The 24h association between PYY and ghrelin at baseline (p = 0.04) was weakened at post (p = 0.14); however, the ghrelin/PYY lunch ratio increased (p = 0.01) indicating the potential for ghrelin predominance over PYY in the circulation. PYY and ghrelin are reciprocally associated during a period of weight stability, but not following weight loss. An "uncoupling" may have occurred, particularly at lunch, due to factors that modulate ghrelin in response to weight loss.

Topics: Adult; Body Composition; Body Weight; Female; Ghrelin; Humans; Leptin; Peptide YY; Premenopause; Weight Loss; Young Adult

Reducing dietary energy density (ED) promotes weight loss; however, underlying mechanisms are not well understood. The purpose of this study was to determine if low-ED diets facilitate weight loss through actions on ghrelin and peptide YY (PYY), independent of influences of psychosocial measures. Seventy-one obese women (BMI 30-40 kg/m(2)) ages 22-60 years received counseling to reduce ED. Fasting blood samples were analyzed for total ghrelin and total PYY by radioimmunoassay at months 0, 3, 6, and 12. Restraint, disinhibition, and hunger were assessed by the Eating Inventory. Body weight (-7.8 ± 0.5 kg), BMI (-2.9 ± 0.2 kg/m(2)), body fat (-3.0 ± 0.3%), and ED (-0.47 ± 0.05 kcal/g or -1.97 ± 0.21 kJ/g) decreased from months 0 to 6 (p<0.05) after which no change occurred from months 6 to 12. Ghrelin increased in a curvilinear fashion (month 0: 973 ± 39, month 3: 1024 ± 37, month 6: 1109 ± 44, and month 12: 1063 ± 45 pg/ml, p<0.001) and PYY increased linearly (month 0: 74.2 ± 3.1, month 3: 76.4 ± 3.2, month 6: 77.2 ± 3.0, month 12: 82.8 ± 3.2 pg/ml, p<0.001). ED, body weight, and hunger predicted ghrelin, with ED being the strongest predictor (ghrelin = 2674.8+291.6 × ED-19.2 × BW-15 × H; p<0.05). There was a trend toward a significant association between ED and PYY (PYY = 115.0-43.1 × ED; p = 0.05). Reductions in ED may promote weight loss and weight loss maintenance by opposing increases in ghrelin and promoting increases in PYY.

Topics: Adult; Body Mass Index; Energy Metabolism; Female; Ghrelin; Humans; Middle Aged; Obesity; Peptide YY; Weight Loss; Young Adult

This study investigated (a) changes in ghrelin and peptide YY (PYY) concentrations during a weight reduction programme and (b) baseline ghrelin and PYY levels as predictors of weight loss in 32 severely obese adolescents (BMI z score = 4.1). Subjects spent an academic year in an institution for childhood obesity. Fasting ghrelin and PYY, leptin, insulin levels and insulin resistance were measured at baseline (month 0) and during the programme (months 3, 6, 9). In addition, 15 normal-weight teenagers served as reference for the baseline assessments. At baseline, obese teenagers had lower ghrelin and PYY concentrations than normal-weight adolescents (P < 0.05). Moreover, they showed significantly higher leptin, insulin levels and homeostasis model assessment (HOMA) (P < 0.0001). During the lifestyle modification, there was a significant decrease in body weight among obese teenagers, associated with an increase in ghrelin (apparent from month 6; P < 0.05), a decrease in leptin (from month 3; P < 0.05) and a decrease in insulin and HOMA (from month 3; P < 0.0001), without any significant change in PYY. Anthropometrical changes were correlated neither with baseline ghrelin levels nor with changes in ghrelin and PYY after the lifestyle modification. However, higher baseline PYY tended to correlate with greater anthropometrical changes (P < 0.1). In adolescents with severe obesity, a long-term combination of supervised aerobic exercises and a balanced diet led to weight reduction and increased ghrelin concentrations, without any change in PYY concentrations. Moreover, baseline PYY concentrations might be considered as predictors of weight loss.

Topics: Adolescent; Exercise; Exercise Therapy; Female; Ghrelin; Humans; Life Style; Male; Obesity, Morbid; Peptide YY; Weight Loss

The effects of gastric bypass surgery on the secretion of the anorexigenic gut-derived hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), independent of caloric restriction and due to different dietary macronutrients, is not well characterized. This study examines the effects of a mixed-nutrient or high-fat liquid meal on the postprandial stimulation of GLP-1 and PYY following gastric bypass or equivalent hypocaloric diet.. Total PYY and active GLP-1 were measured fasting and at multiple points after standardized mixed-nutrient and high-fat liquid meals in two matched groups of obese subjects. The meal stimulation tests were performed before and 14.6 ± 3.3 days after gastric bypass (GBP, n = 10) and before and after a 7-day hypocaloric liquid diet matching the post-GBP diet (control, n = 10).. Mixed-nutrient and high-fat postprandial GLP-1 levels increased following GBP (mixed-nutrient peak: 85.0 ± 28.6-323 ± 51 pg/ml, P < 0.01; high-fat peak: 81.8 ± 9.6-278 ± 49 pg/ml, P < 0.01), but not after diet (mixed-nutrient peak: 104.4 ± 9.4-114.9 ± 15.8 pg/ml, P = NS; high-fat peak: 118.1 ± 16.4-104.4 ± 10.8 pg/ml, P = NS). The postprandial PYY response also increased after GBP but not diet, though the increase in peak PYY did not reach statistical significance (GBP mixed-nutrient peak: 134.8 ± 26.0-220.7 ± 52.9 pg/ml, P = 0.09; GBP high-fat peak: 142.1 ± 34.6-197.9 ± 12.7 pg/ml, P = 0.07; diet mixed-nutrient peak: 99.8 ± 8.0-101.1 ± 13.3 pg/ml, P = NS; diet high-fat peak: 105.0 ± 8.8-103.1 ± 11.8 pg/ml, P = NS). The postprandial GLP-1 response was not affected by the macronutrient content of the meal. However, following GBP the mixed-nutrient PYY total area under the curve (AUC(0-120)) was significantly greater than the high-fat PYY AUC(0-120) (22,081 ± 5,662 pg/ml min vs. 18,711 ± 1,811 pg/ml min, P = 0.04).. Following GBP there is an increase in the postprandial stimulation of PYY and GLP-1 that is independent of caloric restriction. The phenomenon of "bariatric surgery-induced anorexia" may be linked to the increased levels after GBP.

Topics: Adolescent; Adult; Aged; Appetite; Body Mass Index; Caloric Restriction; Case-Control Studies; Diabetes Mellitus, Type 2; Diet, High-Fat; Fasting; Female; Food; Gastric Bypass; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Obesity, Morbid; Peptide YY; Postprandial Period; Prospective Studies; Weight Loss; Young Adult

Many patients with major depression refer a decreased appetite and weight loss among their symptoms. Peptide YY (PYY) and ghrelin belong to the family of peptides of the gut-brain axis implicated in the regulation of appetite and energy metabolism. PYY stimulates a powerful central satiety response and ghrelin increases food intake and weight gain. Brain-derived neurotrophic factor (BDNF) also contributes to the central control of food intake as an anorexigenic factor.. To study fasting plasma total and acylated ghrelin, plasma PYY and serum BDNF levels in patients with major depression with weight loss as one of their symptoms and compare them with matched healthy controls.. Fifteen adult patients, 9 male and 6 female, with recent diagnosis of major depression, and 16 healthy adult subjects, matched by age and anthropometric parameters were studied. All depressed patients referred weight loss and were not under antidepressant therapy. Fasting total PYY, total ghrelin and acylated ghrelin and BDNF were determined.. Fasting total PYY was higher in patients than controls (2.01±0.09 vs 1.29±0.16 pmol/l). There were no differences in fasting total ghrelin, acylated ghrelin or BDNF levels.. Major depressed patients, with weight loss at diagnosis, showed higher fasting plasma PYY levels that could contribute to their reduced appetite.

Topics: Acetylation; Adult; Appetite Regulation; Body Mass Index; Brain-Derived Neurotrophic Factor; Case-Control Studies; Cohort Studies; Depressive Disorder, Major; Feeding and Eating Disorders; Female; Ghrelin; Humans; Male; Middle Aged; Peptide YY; Self Report; Weight Loss

Roux-en-Y gastric bypass (RYGB) surgery causes profound changes in secretion of gastrointestinal hormones and glucose metabolism. We present a detailed analysis of the early hormone changes after RYGB in response to three different oral test meals designed to provide this information without causing side effects (such as dumping).. We examined eight obese non-diabetic patients before and within 2 weeks after RYGB. On separate days, oral glucose tolerance tests (25 or 50 g glucose dissolved in 200 mL of water) and a liquid mixed meal test (200 mL 300 kcal) were performed. We measured fasting and postprandial glucose, insulin, C-peptide, glucagon, total and intact glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-2 (GLP-2), peptide YY(3-36) (PYY), cholecystokinin (CCK), total and active ghrelin, gastrin, somatostatin, pancreatic polypeptide (PP), amylin, leptin, free fatty acids (FFA), and registered postprandial dumping. Insulin sensitivity was measured by homeostasis model assessment of insulin resistance.. Fasting glucose, insulin, ghrelin, and PYY were significantly decreased and FFA was elevated postoperatively. Insulin sensitivity increased after surgery. The postprandial response increased for C-peptide, GLP-1, GLP-2, PYY, CCK, and glucagon (in response to the mixed meal) and decreased for total and active ghrelin, leptin, and gastrin, but were unchanged for GIP, amylin, PP, and somatostatin after surgery. Dumping symptoms did not differ before and after the operation or between the tests.. Within 2 weeks after RYGB, we found an increase in insulin secretion and insulin sensitivity. Responses of appetite-regulating intestinal hormones changed dramatically, all in the direction of reducing hunger.

Topics: Adult; Appetite; C-Peptide; Cholecystokinin; Confounding Factors, Epidemiologic; Female; Gastric Bypass; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Ghrelin; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Islet Amyloid Polypeptide; Leptin; Male; Middle Aged; Obesity, Morbid; Pancreatic Polypeptide; Peptide YY; Postprandial Period; Somatostatin; Time Factors; Weight Loss

Bariatric surgical procedures, including the laparoscopic adjustable gastric band (LAGB), are currently the only effective treatments for morbid obesity, however, there is no clear understanding of the mechanisms underpinning the efficacy of LAGB. The aim of this study is to examine changes in activation of the sensory neuronal pathways and levels of circulating gut hormones associated with inflation of an AGB.. The trajectory within the central nervous system of polysynaptic projections of sensory neurons innervating the stomach was determined using the transsynaptically transported herpes simplex virus (HSV). Populations of HSV-infected neurons were present in the brainstem, hypothalamus and cortical regions associated with energy balance. An elevation of Fos protein was present within the nucleus of the solitary tract, a region of the brainstem involved in the control of food intake, following acute and chronic band inflation. Two approaches were used to test (1) the impact of inflation of the band alone (on a standard caloric background) or (2) the impact of a standard caloric meal (on the background of the inflated band) on circulating gut hormones. Importantly, there was a significant elevation of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) following oral gavage of a liquid meal in animals with pre-inflated bands. There was no impact of inflation of the band alone on circulating GLP-1, PYY or ghrelin in animals on a standard caloric background.. These data are consistent with the notion that the LAGB exerts its effects on satiety, reduced food intake and reduced body weight by the modulation of both neural and hormonal responses with the latter involving an elevation of meal-related levels of GLP-1 and PYY. These data are contrary to the view that the surgery is purely 'restrictive'.

Topics: Animals; Brain; Caloric Restriction; Disease Models, Animal; Eating; Gastric Mucosa; Gastroplasty; Ghrelin; Glucagon-Like Peptide 1; Laparoscopy; Male; Obesity, Morbid; Peptide YY; Rats; Rats, Sprague-Dawley; Satiation; Sensory Receptor Cells; Signal Transduction; Simplexvirus; Stomach; Weight Loss

Losing weight can pose a challenge, but how to avoid putting those pounds back on can be a real struggle. A major health problem for obese people is that diseases linked to obesity, such as type 2 diabetes and cardiovascular disease, put their lives at risk, even in young individuals. Although bariatric surgery-a surgical method to reduce or modify the gastrointestinal tract-was originally envisioned for the most severe cases of obesity, evidence suggests that the benefit of this procedure may not be limited to the staggering weight loss it causes. Endogenous factors released from the gut, and modified after surgery, may explain why bariatric surgery can be beneficial for obesity-related diseases and why operated individuals successfully maintain the weight loss. In 'Bedside to Bench,' Rachel Larder and Stephen O'Rahilly peruse a human study with dieters who regained weight despite a successful diet. Appetite-regulating hormones in the gut may be responsible for this relapse in the long term. In 'Bench to Bedside,' Keval Chandarana and Rachel Batterham examine how two different methods of bariatric surgery highlight the relevance of gut-derived hormones not only in inducing sustained weight loss but also in improving glucose homeostasis. These insights may open new avenues to bypass the surgery and obtain the same results with targeted drugs.

Topics: Bariatric Surgery; Cholecystokinin; Glucagon-Like Peptide 1; Glucose; Humans; Obesity; Peptide YY; Weight Loss

Losing weight can pose a challenge, but how to avoid putting those pounds back on can be a real struggle. A major health problem for obese people is that diseases linked to obesity, such as type 2 diabetes and cardiovascular disease, put their lives at risk, even in young individuals. Although bariatric surgery-a surgical method to reduce or modify the gastrointestinal tract-was originally envisioned for the most severe cases of obesity, evidence suggests that the benefit of this procedure may not be limited to the staggering weight loss it causes. Endogenous factors released from the gut, and modified after surgery, may explain why bariatric surgery can be beneficial for obesity-related diseases and why operated individuals successfully maintain the weight loss. In 'Bedside to Bench,' Rachel Larder and Stephen O'Rahilly peruse a human study with dieters who regained weight despite a successful diet. Appetite-regulating hormones in the gut may be responsible for this relapse in the long term. In 'Bench to Bedside,' Keval Chandarana and Rachel Batterham examine how two different methods of bariatric surgery highlight the relevance of gut-derived hormones not only in inducing sustained weight loss but also in improving glucose homeostasis. These insights may open new avenues to bypass the surgery and obtain the same results with targeted drugs.

Topics: Bariatric Surgery; Diabetes Mellitus, Type 2; Gastric Bypass; Humans; Obesity; Peptide YY; Weight Loss

Gastric bypass leads to the remission of type 2 diabetes independently of weight loss. Our hypothesis is that changes in bile flow due to the altered anatomy may partly explain the metabolic outcomes of the operation. We prospectively studied 12 patients undergoing gastric bypass and six patients undergoing gastric banding over a 6-wk period. Plasma fibroblast growth factor (FGF)19, stimulated by bile acid absorption in the terminal ileum, and plasma bile acids were measured. In canine and rodent models, we investigated changes in the gut hormone response after altered bile flow. FGF19 and total plasma bile acids levels increased after gastric bypass compared with no change after gastric banding. In the canine model, both food and bile, on their own, stimulated satiety gut hormone responses. However, when combined, the response was doubled. In rats, drainage of endogenous bile into the terminal ileum was associated with an enhanced satiety gut hormone response, reduced food intake, and lower body weight. In conclusion, after gastric bypass, bile flow is altered, leading to increased plasma bile acids, FGF19, incretin. and satiety gut hormone concentrations. Elucidating the mechanism of action of gastric bypass surgery may lead to novel treatments for type 2 diabetes.

Topics: Adult; Animals; Bile; Bile Acids and Salts; Blood Glucose; C-Reactive Protein; Calorimetry; Diabetes Mellitus, Type 2; Dogs; Female; Fibroblast Growth Factors; Gastric Bypass; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Peptide YY; Rats; Rats, Wistar; Weight Loss

To investigate the relationship between the function of vagus nerve and peptide YY(3-36) and ghrelin levels after subtotal gastrectomy.. We enrolled a total of 16 patients who underwent subtotal gastrectomy due to gastric cancer. All surgeries were performed by a single skilled surgeon. We measured peptide YY(3-36), ghrelin, leptin, insulin, growth hormone levels, and body weight immediately before and one month after surgery.. Vagus nerve preservation group showed less body weight loss and less increase of peptide YY(3-36) compared with vagotomy group (-5.56 ± 2.24 kg vs -7.85 ± 1.57 kg, P = 0.037 and 0.06 ± 0.08 ng/mL vs 0.19 ± 0.12 ng/mL, P = 0.021, respectively). Moreover, patients with body weight loss of less than 10% exhibited reduced elevation of peptide YY(3-36) level, typically less than 20% [6 (66.7%) vs 0 (0.0%), P = 0.011, odd ratio = 3.333, 95% confidence interval (1.293, 8.591)].. Vagus nerve preservation contributes to the maintenance of body weight after gastrectomy, and this phenomenon may be related to the suppressed activity of peptide YY(3-36).

Topics: Adenocarcinoma; Aged; Body Weight; Female; Gastrectomy; Ghrelin; Humans; Male; Middle Aged; Organ Sparing Treatments; Peptide YY; Stomach Neoplasms; Vagotomy; Vagus Nerve; Weight Loss

Significant weight loss following Roux-en-Y gastric bypass surgery (RYGB) in obese humans correlates with enhanced secretion of anorexigenic gut hormones glucagon-like peptide-1 (GLP-1) and peptide YY(3-36) (PYY(3-36)). Our aim here was to identify a dosing strategy for intraperitoneal (IP) infusion of GLP-1 homologue exendin-4 alone and with PYY(3-36) that produces a sustained reduction in daily food intake and body weight in diet-induced obese (DIO) rats. We tested 12 exendin-4 strategies over 10 weeks. Exendin-4 infused during the first and last 3 h of the dark period at 15-20 pmol/h (0.15 nmol/kg/day) produced a sustained 24 ± 1% reduction in daily food intake for 17 days, and decreased body weight by 7%. In a separate group of DIO rats, none of seven dosing strategies combining exendin-4 and PYY(3-36) produced a similar reduction in daily food intake for >10 days. The subsequent decline in efficacies of exendin-4 alone and with PYY(3-36) on food intake and body weight in each experiment suggested possible receptor downregulation and tolerance to treatments. However, when treatments were discontinued for 1 day following losses in efficacies, daily food intake significantly increased. Together, these results demonstrate that (i) intermittent IP infusion of a low dose of exendin-4 can produce a relatively prolonged reduction in daily food intake and body weight in DIO rats, (ii) co-infusion of exendin-4 and PYY(3-36) does not further prolong this response, and (iii) activation of an orexigenic mechanism gradually occurs to counteract the inhibitory effects of exendin-4 alone and with PYY(3-36) on food intake and body weight.

Topics: Animals; Body Weight; Diet; Dose-Response Relationship, Drug; Drug Combinations; Drug Evaluation, Preclinical; Eating; Exenatide; Hypoglycemic Agents; Male; Obesity; Peptide Fragments; Peptide YY; Peptides; Rats; Rats, Sprague-Dawley; Venoms; Weight Loss

Bariatric surgery causes durable weight loss. Gut hormones are implicated in obesity pathogenesis, dietary failure, and mediating gastrointestinal bypass (GIBP) surgery weight loss. In mice, we determined the effects of diet-induced obesity (DIO), subsequent dieting, and GIBP surgery on ghrelin, peptide YY (PYY), and glucagon-like peptide-1 (GLP-1). To evaluate PYY's role in mediating weight loss post-GIBP, we undertook GIBP surgery in PyyKO mice.. Male C57BL/6 mice randomized to a high-fat diet or control diet were killed at 4-week intervals. DIO mice underwent switch to ad libitum low-fat diet (DIO-switch) or caloric restriction (CR) for 4 weeks before being killed. PyyKO mice and their DIO wild-type (WT) littermates underwent GIBP or sham surgery and were culled 10 days postoperatively. Fasting acyl-ghrelin, total PYY, active GLP-1 concentrations, stomach ghrelin expression, and colonic Pyy and glucagon expression were determined. Fasting and postprandial PYY and GLP-1 concentrations were assessed 30 days postsurgery in GIBP and sham pair-fed (sham.PF) groups.. DIO progressively reduced circulating fasting acyl-ghrelin, PYY, and GLP-1 levels. CR and DIO-switch caused weight loss but failed to restore circulating PYY to weight-appropriate levels. After GIBP, WT mice lost weight and exhibited increased circulating fasting PYY and colonic Pyy and glucagon expression. In contrast, the acute effects of GIBP on body weight were lost in PyyKO mice. Fasting PYY and postprandial PYY and GLP-1 levels were increased in GIBP mice compared with sham.PF mice.. PYY plays a key role in mediating the early weight loss observed post-GIBP, whereas relative PYY deficiency during dieting may compromise weight-loss attempts.

Topics: Analysis of Variance; Animals; Colon; Diet, Fat-Restricted; Diet, Reducing; Enzyme-Linked Immunosorbent Assay; Gastric Bypass; Gastric Mucosa; Ghrelin; Glucagon; Glucagon-Like Peptide 1; Leptin; Male; Mice; Obesity; Peptide YY; Radioimmunoassay; Random Allocation; Reverse Transcriptase Polymerase Chain Reaction; Weight Loss

Roux-en-Y gastric bypass (RYGB) imparts long-term weight loss, the mechanisms for which are not well understood. Changes in leptin and gastrointestinal (GI) hormones, including glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and ghrelin, may contribute to the relative success of RYGB compared with conventional weight loss methods. This study evaluated changes in GI hormones and leptin post-RYGB. The study also evaluated whether GI hormones differed after a short-term dose of protein or fat.. GLP-1, PYY, ghrelin, and leptin were assessed in 16 women before RYGB and up to 1 year after RYGB. Plasma was collected before and at several times after a short-term equicaloric dose of protein or fat.. GLP-1 area under the curve (AUC) increased at week 6 and 1 year in the fat beverage (FAT-BEV) group compared with baseline. PYY AUC remained elevated at 1 year in the FAT-BEV group. Ghrelin AUC decreased at week 2, week 6, and 1 year in the protein beverage (PRO-BEV) group compared with baseline. Ghrelin AUC was lower in the PRO-BEV group compared with the FAT-BEV group at week 6. Fasted leptin decreased at all visits in both groups and was lower in the FAT-BEV group compared with the PRO-BEV group at 1 year.. Changes from baseline were evident for all GI hormones and leptin; some differences were evident soon after surgery (ghrelin, leptin), whereas others were maintained long term (GLP-1, PYY, ghrelin, leptin). In response to a short-term stimulus, protein suppressed ghrelin and fat potently stimulated GLP-1 and PYY. Future work in this area is warranted.

Topics: Adult; Area Under Curve; Dietary Fats; Dietary Proteins; Female; Gastric Bypass; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Leptin; Middle Aged; Obesity, Morbid; Peptide YY; Postoperative Period; Weight Loss

Weight-loss independent mechanisms may play an important role in the improvement of glucose homeostasis after Roux-en-Y gastric bypass (RYGB). The objective of this analysis was to determine whether RYGB causes greater improvement in glucostatic parameters as compared with laparoscopic adjustable gastric banding (LAGB) or low calorie diet (LCD) after equivalent weight loss and independent of enteral nutrient passage. Study 1 recruited participants without type 2 diabetes mellitus (T2DM) who underwent LAGB (n = 8) or RYGB (n = 9). Study 2 recruited subjects with T2DM who underwent LCD (n = 7) or RYGB (n = 7). Insulin-supplemented frequently-sampled intravenous glucose tolerance test (fsIVGTT) was performed before and after equivalent weight reduction. MINMOD analysis of insulin sensitivity (Si), acute insulin response to glucose (AIRg) and C-peptide (ACPRg) response to glucose, and insulin secretion normalized to the degree of insulin resistance (disposition index (DI)) were analyzed. Weight loss was comparable in all groups (7.8 ± 0.4%). In Study 1, significant improvement of Si, ACPRg, and DI were observed only after LAGB. In Study 2, Si, ACPRg, and plasma adiponectin increased significantly in the RYGB-DM group but not in LCD. DI improved in both T2DM groups, but the absolute increase was greater after RYGB (258.2 ± 86.6 vs. 55.9 ± 19.9; P < 0.05). Antidiabetic medications were discontinued after RYGB contrasting with 55% reduction in the number of medications after LCD. No intervention affected fasting glucagon-like peptide (GLP)-1, peptide YY (PYY) or ghrelin levels. In conclusion, RYGB produced greater improvement in Si and DI compared with diet at equivalent weight loss in T2DM subjects. Such a beneficial effect was not observed in nondiabetic subjects at this early time-point.

Topics: Adiponectin; Adult; Blood Glucose; C-Peptide; Caloric Restriction; Diabetes Mellitus, Type 2; Diet, Reducing; Female; Gastric Bypass; Ghrelin; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Laparoscopy; Male; Middle Aged; Obesity; Peptide YY; Weight Loss

Unknown hormonal and neural satiety signals are thought to drive sustainable weight loss following laparoscopic adjustable gastric banding (LAGB). The objective of this study was to investigate whether the structurally related satiety hormones pancreatic polypeptide (PP) and peptide YY (PYY) influence total percentage weight loss after LAGB.. A cross-sectional study examined 17 postoperative individuals who had already achieved a mean of 28% LAGB-induced weight loss (range, 10-38%). A prospective study assessed plasma PP and PYY meal responses in 16 obese individuals prior to LAGB.. In the cross-sectional study, individuals with higher weight loss had lower PP meal responses (2-h AUC, R = -0.60, p = 0.01) and lower fasting PYY levels (R = -0.55, p = 0.02). In the prospective study, subsequent mean weight loss was 20% (range, 5-50%) after a mean of 53 months. Low preoperative PP meal response (2-h AUC) predicted significantly higher subsequent weight loss after LAGB (R = -0.56, p = 0.024). The eight individuals with the lowest PP meal response lost more weight than the eight with the highest PP meal response (median 25% vs. 14%, p = 0.004). When compared across all three groups, mean PP meal responses did not differ. Fasting PYY levels, however, were significantly lower in the postoperative group compared to the group tested pre-operatively, or the BMI-matched controls (-30%, p = 0.03).. PYY appears reduced in proportion to weight loss following LAGB, possibly representing attempted orexigenic homeostatic compensation. Although PP responses appear unchanged by weight loss status, low PP meal response may predict higher weight loss. PP meal response may be a biological marker that could predict an individual's susceptibility to the mechanism underlying LAGB-induced weight loss.

Topics: Adult; Cross-Sectional Studies; Female; Gastroplasty; Humans; Male; Obesity; Pancreatic Polypeptide; Peptide YY; Postprandial Period; Prospective Studies; Weight Loss

Bariatric surgery is currently the most effective and durable treatment option for extreme obesity. Restrictive procedures, such as AGB and SG, limit gastric capacity and, thus, food intake while leaving the gastrointestinal tract intact. Malabsorptive procedures, such as BPD, shorten the length of the intestine to decrease nutrient absorption. Combined procedures, such as RYGB, include restriction and gastrointestinal rearrangement. Procedures that bypass segments of the gut are associated with greater weight loss and greater improvements in comorbid conditions than is gastric banding. This may be due, in part, to the differential effects of gastrointestinal rearrangement on the secretion of orexigenic and anorexigenic gut peptides that regulate appetite, glucose homeostasis, and body weight. Bariatric surgery is generally associated with low rates of perioperative and postoperative morbidity and mortality, although rigorous comparative safety data are lacking. High-quality, long-term, randomized, controlled trials are needed to compare the efficacy, safety, and cost effectiveness of the various bariatric surgery procedures with each other, as well as with intensive nonsurgical weight loss interventions.

Topics: Anastomosis, Roux-en-Y; Bariatric Surgery; Biliopancreatic Diversion; Endoscopy, Digestive System; Ghrelin; Glucagon-Like Peptide 1; Humans; Obesity; Peptide YY; Treatment Outcome; Weight Loss

Bariatric surgery is the most effective treatment option for obesity, and gut hormones are implicated in the reduction of appetite and weight after Roux-en-Y gastric bypass. Although there is increasing interest in the gut hormone changes after gastric bypass, the long-term changes have not been fully elucidated.. Thirty-four participants were studied cross-sectionally at four different time points, pre-operatively (n = 17) and 12 (n = 6), 18 (n = 5) and 24 months (n = 6) after laparoscopic Roux-en-Y gastric bypass. Another group of patients (n = 6) were studied prospectively (18-24 months). All participants were given a standard 400 kcal meal after a 12-h fast, and plasma levels of peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) were correlated with changes in appetite over 3 h using visual analogue scores.. The post-operative groups at 12, 18 and 24 months had a higher post-prandial PYY response compared to pre-operative (p < 0.05). This finding was confirmed in the prospective study at 18 and 24 months. There was a trend for increasing GLP-1 response at 18 and 24 months, but this did not reach statistical significance (p = 0.189) in the prospective study. Satiety was significantly reduced in the post-operative groups at 12, 18 and 24 months compared to pre-operative levels (p < 0.05).. Roux-en-Y gastric bypass causes an enhanced gut hormone response and increased satiety following a meal. This response is sustained over a 24-month period and may partly explain why weight loss is maintained.

Topics: Adult; Cross-Sectional Studies; Female; Gastric Bypass; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Obesity, Morbid; Peptide YY; Postoperative Period; Prospective Studies; Satiety Response; Weight Loss

The effects of medical and surgical treatments for obesity on peptide YY (PYY) levels, in patients with similar weight loss, remain unclear.. The objective of the study was to assess PYY and appetite before and after Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and medical treatment (MED).. This was a prospective, controlled, nonrandomized study.. The study was conducted at the Departments of Nutrition and Digestive Surgery at a university hospital.. PARTICIPANTS included three groups of eight patients with similar body mass indexes (RYGB 37.8 +/- 0.8, SG 35.3 +/- 0.7, and MED 39.1 +/- 1.7 kg/m(2), P = NS) and eight lean controls (body mass index 21.7 +/- 0.7 kg/m(2)).. Total plasma PYY, hunger, and satiety visual analog scales in fasting and after ingestion of a standard test meal were measured.. At baseline there were no differences in the area under the curve (AUC) of PYY, hunger, or satiety in obese groups. Two months after the interventions, RYGB, SG, and MED groups achieved similar weight loss (17.7 +/- 3, 14.9 +/- 2.4, 16.6 +/- 4%, respectively, P = NS). PYY AUC increased in RYGB (P < 0.001) and SG (P < 0.05) and did not change in MED. PYY levels decreased at fasting, 30 min, and 180 min after a standard test meal in MED (P < 0.05). Hunger AUC decreased in RYGB (P < 0.05). Satiety AUC increased in RYGB (P < 0.05) and SG (P < 0.05). Appetite did not change in MED. PYY AUC correlated with satiety AUC (r = 0.35, P < 0.05).. RYGB and SG increased PYY and reduced appetite. MED failed to produce changes. Different effects occur despite similar weight loss. This suggests that the weight-loss effects of these procedures are enhanced by an increase in PYY and satiety.

Topics: Adult; Analysis of Variance; Area Under Curve; Body Mass Index; Diet Therapy; Exercise; Female; Gastrectomy; Gastric Bypass; Humans; Hunger; Male; Middle Aged; Obesity; Patient Selection; Peptide YY; Prospective Studies; Radioimmunoassay; Regression Analysis; Satiation; Time Factors; Weight Loss

The aim of this study was to evaluate whether gastric bypass with or without vagal preservation resulted in a different outcome.. Body weight, food intake and postprandial peptide YY (PYY) and glucagon-like peptide (GLP-1) levels were compared between gastric bypass (n = 55) and sham-operated rats (n = 27) in three groups. In group 1 (n = 17), the vagal nerve was not preserved, while in group 2 the vagal nerve was preserved during gastric bypass (n = 10). In group 3, gastric bypass rats (n = 28) were randomised for either one of the two techniques.. Rats in which the vagal nerve was preserved during gastric bypass showed a lower body weight (p < 0.001) and reduced food intake (p < 0.001) compared to rats in which the vagal nerve was not preserved during the gastric bypass operation. Levels of PYY and GLP-1 were significantly increased after gastric bypass compared to sham-operated controls (p < 0.05), but there was no difference between gastric bypass rats with and without vagal preservation. Differences in food intake and body weight were not related to the size of the gastro-jejunostomy in gastric bypass rats. There were no signs of malabsorption or inflammation after gastric bypass.. We propose that the vagal nerve should be preserved during the gastric bypass operation as this might play an important role for the mechanisms that induce weight loss and reduce food intake in rats. In contrast, the gastro-jejunal stoma size was found to be of minor relevance.

Topics: Animals; Gastric Bypass; Gastrostomy; Glucagon-Like Peptide 1; Jejunostomy; Male; Obesity, Morbid; Peptide YY; Postprandial Period; Random Allocation; Rats; Rats, Wistar; Treatment Outcome; Vagus Nerve; Weight Loss

The gut hormone PYY3-36 influences food intake and body weight via interaction with hypothalamic presynaptic Y2 receptors (Y2R). Novel Y2R-selective analogues of PYY3-36 are therefore potential drug candidates for the treatment of obesity. It has been hypothesized that PYY3-36 and possibly also the related PP-fold peptides, NPY and PP, bind to the membrane via their amphipathic alpha-helix prior to receptor interaction. The PYY3-36 amphipathic alpha-helix causes the peptide to associate with the membrane, making it essential for Y receptor potency as it potentially guides the C-terminal pentapeptide into the correct conformation for receptor activation. Based on this hypothesis, the importance of the amphipathic nature of PYY3-36, as well as the ability of amphipathic alpha-helices to interact in solution to form di- and tetramers, we redesigned the peptide architecture by addition of an amphipathic alpha-helix via the Lys 4 side chain of PYY3-36. Two different amphipathic sequences were introduced; first, PYY17-31, the native alpha-helix of PYY, and secondly, its retro counterpart, PYY31-17, which is also predicted to form an alpha-helix. Moreover, several different turn motifs between the branching point and the additional alpha-helix were tested. Several novel peptides with nanomolar Y2R binding affinities, as well as increased Y receptor selectivity, were identified. CD experiments showed the modifications to be well accepted, and an increase in mean ellipticity (ME) signifying an increased degree of alpha-helicity was observed. Receptor binding experiments indicated that the direction of the additional alpha-helix is less important, in contrast to the turn motifs, which greatly affect the Y1R binding and thus determine the Y1R activity. Conversely, the structure-activity relationships from in vivo data showed that the peptide containing the retro-sequence was inactive, even though the binding data demonstrated high affinity and selectivity. This demonstrates that radical redesign of peptide architecture can provide nanomolar binding with improved subtype selectivity and with in vivo efficacy.

Topics: Amino Acid Sequence; Animals; Anti-Obesity Agents; Cell Line; Circular Dichroism; Humans; Male; Mice; Molecular Sequence Data; Peptide YY; Peptides; Protein Binding; Protein Structure, Secondary; Structure-Activity Relationship; Weight Loss

Bariatric surgery has been shown to reverse type 2 diabetes; however, mechanisms by which this occurs remain undefined. Ileal interposition (IT) is a surgical model that isolates the effects of increasing delivery of unabsorbed nutrients to the lower gastrointestinal tract. In this study we investigated effects of IT surgery on glucose tolerance and diabetes onset in UCD-T2DM (University of California at Davis type 2 diabetes mellitus) rats, a polygenic obese animal model of type 2 diabetes.. IT or sham surgery was performed on 4-month-old male UCD-T2DM rats. All animals underwent oral glucose tolerance testing (OGTT). A subset was killed 2 months after surgery for tissue analyses. The remainder was followed until diabetes onset and underwent oral fat tolerance testing (OFTT).. IT surgery delayed diabetes onset by 120 +/- 49 days compared with sham surgery (P < .05) without a difference in body weight. During OGTT, IT-operated animals exhibited lower plasma glucose excursions (P < .05), improved early insulin secretion (P < .01), and 3-fold larger plasma glucagon-like peptide-1(7-36) (GLP-1(7-36)) excursions (P < .001), and no difference in glucose-dependent insulinotropic polypeptide responses compared with sham-operated animals. Total plasma peptide YY (PYY) excursions during OFTT were 3-fold larger in IT-operated animals (P < .01). IT-operated animals exhibited lower adiposity (P < .05), smaller adipocyte size (P < .05), 25% less ectopic lipid deposition, lower circulating lipids, and greater pancreatic insulin content compared with sham-operated animals (P < .05).. IT surgery delays the onset of diabetes in UCD-T2DM rats which may be related to increased nutrient-stimulated secretion of GLP-1(7-36) and PYY and improvements of insulin sensitivity, beta-cell function, and lipid metabolism.

Topics: Adipocytes; Adiponectin; Animals; Diabetes Mellitus, Type 2; Gastric Bypass; Glucagon-Like Peptide 1; Glucose; Ileum; Insulin; Lipid Metabolism; Male; Peptide YY; Rats; Weight Loss

To compare the effects of weight loss by an energy-restricted low-fat diet vs low-carbohydrate diet on serum peptide YY (PYY) levels.. 8-Week prospective study of 30 obese adults (mean age: 42.8+/-2.0 years, mean body mass index 35.5+/-0.6 kg m(-2)).. After 8 weeks, subjects on the low-carbohydrate diet lost substantially more weight than those on the low-fat diet (5.8 vs 0.99 kg, P<0.001). Weight loss by either diet resulted in a 9% reduction in both mean fasting serum PYY levels (baseline: 103.5+/-8.8 pg ml(-1), after weight loss: 94.1+/-6.5 pg ml(-1), P<0.01) and postprandial area under the curve (AUC) PYY (baseline: (20.5+/-1.5) x 10(3) pg h(-1) ml(-1), after weight loss: mean AUC PYY (18.8+/-1.4) x 10(3) pg h(-1) ml(-1), P<0.001). There was a trend towards lower levels of PYY with greater degrees of weight loss.. Reduced PYY levels after weight loss by an energy-restricted low-fat or low-carbohydrate diet likely represents a compensatory response to maintain energy homeostasis and contributes to difficulty in weight loss during energy-restricted diets.

Topics: Adult; Body Mass Index; Diet, Carbohydrate-Restricted; Diet, Fat-Restricted; Diet, Reducing; Female; Humans; Male; Obesity; Peptide YY; Postprandial Period; Prospective Studies; Weight Loss

Roux-en-Y gastric bypass (RYGB) surgery is one of the most effective treatments for obesity producing long-term weight loss. The anorexia and weight loss from RYGB could be due to gastric restriction, malabsorption, enhanced lower gut stimulation, increased energy expenditure, and/or other metabolic adaptations. In ileal transposition (IT) surgery, a segment of the ileum is transposed to the upper jejunum with no gastric restriction or malabsorption. Our objective is to compare the effects of RYGB and IT surgeries on food intake, body weight, and plasma concentrations of the anorexigenic lower gut hormone Peptide YY (PYY) in rats.. Adult male Sprague-Dawley rats were subjected to either RYGB (n = 9), IT (n = 9) or sham surgeries (n = 16). A subset of sham animals were either pair-fed to RYGB (n = 9) or ad lib fed (n = 7) on a highly palatable mixed nutrient liquid food (Ensure). Food intake, body weight and plasma PYY concentrations were measured.. The data demonstrate that (1) RYGB produces a sustained reduction in food intake and weight gain, (2) the anorexic effects of IT are relatively transient lasting for 5 weeks, (3) the reduction in weight gain resulting from IT is similar to that of animals pair-fed to RYGB, and (4) RYGB and IT surgeries are associated with elevated postprandial plasma PYY concentrations.. We demonstrate in our rat models that RYGB surgery produces a greater reduction in food intake and weight gain than IT surgery, and that both surgeries are associated with enhanced plasma concentrations of Peptide YY.

Topics: Animals; Bariatric Surgery; Body Weight; Eating; Gastric Bypass; Ileum; Jejunum; Male; Peptide YY; Rats; Rats, Sprague-Dawley; Weight Loss

No prospective study on the long-term effects of gastric resection on gastrointestinal hormonal changes in patients with normal body weight has been reported. The aim of this study was to evaluate the 1-year effect of subtotal gastrectomy on ghrelin and peptide YY (PYY)(3-36) levels.. Eighteen patients with early gastric cancer underwent subtotal gastrectomy with Billroth I reconstruction. We assessed appetite, food intake, body composition, and ghrelin and PYY(3-36) levels preoperatively and 1 year after surgery.. There were no significant difference in the preoperative daily food intake and 1 year after subtotal gastrectomy. Weight loss occurred in all study subjects; 11.7% (n=2), 55.5% (n=10) and 33.3% (n=6) of the patients lost <5%, 5-10% and >10% of their preoperative body weight, respectively. Body mass index, waist circumference and body fat significantly decreased 1 year after subtotal gastrectomy. There were no significant differences in the appetite visual analogue scale preoperatively and 1 year after subtotal gastrectomy. The plasma ghrelin concentration decreased significantly (P=0.006), whereas PYY(3-36) did not show a significant change 1 year after subtotal gastrectomy.. Ghrelin levels and body fat decreased significantly, whereas PYY(3-36) levels as well as appetite and food intake did not change significantly 1 year after subtotal gastrectomy with normal body weight. These findings suggest that decreased ghrelin might contribute directly to reduced body fat.

Topics: Adipose Tissue; Aged; Appetite; Body Mass Index; Energy Intake; Female; Gastrectomy; Ghrelin; Humans; Ideal Body Weight; Male; Middle Aged; Pain Measurement; Peptide YY; Poisson Distribution; Postoperative Complications; Prospective Studies; Time; Waist Circumference; Weight Loss

The last decade has witnessed a marked increase in our understanding of the importance of gut hormones in the regulation of energy homeostasis. In particular, the discovery that the gut hormone peptide YY 3-36 (PYY3-36) reduced feeding in obese rodents and humans fuelled interest in the role of PYY3-36 in body weight regulation. Pharmacological and genetic approaches have revealed that the Y2-receptor mediates the anorectic effects of PYY3-36 whilst mechanistic studies in rodents identified the hypothalamus, vagus and brainstem regions as potential sites of action. More recently, using functional brain imaging techniques in humans, PYY3-36 was found to modulate neuronal activity within hypothalamic and brainstem, and brain regions involved in reward processing. Several lines of evidence suggest that low circulating PYY concentrations predispose towards the development and or maintenance of obesity. Subjects with reduced postprandial PYY release exhibit lower satiety and circulating PYY levels that correlate negatively with markers of adiposity. In addition, mice lacking PYY are hyperphagic and become obese. Conversely, chronic PYY3-36 administration to obese rodents reduces adiposity, and transgenic mice with increased circulating PYY are resistant to diet-induced obesity. Moreover, there is emerging evidence that PYY3-36 may partly mediate the reduced appetite and weight loss benefits observed post-gastric bypass surgery. Taken together these findings, coupled with the retained responsiveness of obese subjects to the effects of PYY3-36, suggest that targeting the PYY system may offer a therapeutic strategy to help treat obesity.

Topics: Animals; Appetite Regulation; Eating; Energy Metabolism; Gastric Bypass; Humans; Obesity; Peptide Fragments; Peptide YY; Receptors, Gastrointestinal Hormone; Weight Loss

The Study of the Effects of Diet on Metabolism and Nutrition (STEDMAN) Project uses comprehensive metabolic profiling to probe biochemical mechanisms of weight loss in humans. Measurements at baseline, 2 and 4 weeks, 6 and 12 months included diet, body composition, metabolic rate, hormones, and 80 intermediary metabolites measured by mass spectrometry. In 27 obese adults in a behavioral weight loss intervention, median weight decreased 13.9 lb over the first 6 months, then reverted towards baseline by 12 months. Insulin resistance (HOMA) was partially ameliorated in the first 6 months and showed sustained improvement at 12 months despite weight regain. Ghrelin increased with weight loss and reverted to baseline, whereas leptin and PYY fell at 6 months and remained persistently low. NPY levels did not change. Factors possibly contributing to sustained improvement in insulin sensitivity despite weight regain include adiponectin (increased by 12 months), IGF-1 (increased during weight loss and continued to increase during weight regain), and visceral fat (fell at 6 months but did not change thereafter). We observed a persistent reduction in free fatty acids, branched chain amino acids, and related metabolites that may contribute to improved insulin action. These findings provide evidence for sustained benefits of weight loss in obese humans and insights into mechanisms.

Topics: Adiponectin; Adult; Behavior Therapy; Biomarkers; Body Weight; Diet; Energy Metabolism; Female; Ghrelin; Humans; Insulin Resistance; Insulin-Like Growth Factor I; Leptin; Middle Aged; Neuropeptide Y; Obesity; Peptide YY; Weight Gain; Weight Loss

The impact of bariatric surgery on levels of peptide YY (PYY) and ghrelin is still under discussion. We undertook a simultaneous evaluation of the serum changes in PYY and ghrelin depending on the specific type of bariatric surgery.. Total PYY and ghrelin were analyzed in 29 healthy persons and in morbidly obese persons undergoing open biliopancreatic diversion (BPD) of Scopinaro (n = 38) or laparoscopic Roux-en-Y gastric bypass (RYGB; n = 13).. RYGB resulted in a significantly greater loss of weight and body mass index than BPD. Both RYGB and BPD were associated with a significant increase in PYY, significantly greater for BDP (p = 0.001). Ghrelin rose significantly after RYGB (p = 0.022) but not after BPD. After surgery, PYY correlated positively with weight (r = 0.416, p = 0.009). Ghrelin did not correlate significantly with any of the variables studied. Analysis of variance showed that only the type of surgery contributed significantly to explain the variances in the PYY (p = 0.002) and ghrelin (p = 0.018).. BPD results in a greater increase in PYY and a lower weight loss than RYGB. However, only RYGB was associated with a significant increase in ghrelin. The differing weight loss according to the type of bariatric surgery does not seem to be explained by changes arising in PYY and ghrelin.

Topics: Adult; Biliopancreatic Diversion; Body Mass Index; Female; Gastric Bypass; Ghrelin; Humans; Male; Middle Aged; Obesity, Morbid; Peptide YY; Treatment Outcome; Weight Loss

The marked weight loss induced by Roux-en-Y gastric bypass (RYGBP) for morbid obesity is still incompletely understood. It has been suggested that, besides the restriction imposed by the surgical procedure, alterations in gut regulatory peptides signaling the brain might contribute. The aim of this study was to measure the putative satiety peptides peptide YY (PYY), glucagon-like peptide-1 (GLP-1), pancreatic polypeptide (PP) and pro-neurotensin (pro-NT) in response to fasting and feeding.. The study is a cross-sectional study. After a prolonged overnight 14 h fast, a standardized mixed meal (574 kcal) was provided. Blood samples for peptide measurements were obtained before and after the meal.. Forty subjects (20 males and females) were included; 10 morbidly obese; (mean age 41+/-7 years; mean BMI 44+/-3 kg/m(2)), 10 operated with RYGBP (age 45+/-5 years; BMI 35+/-6 kg/m(2)), 10 aged-matched lean (age 44+/-5 years; BMI 24+/-3 kg/m(2)) and 10 young lean subjects (age 26+/-2 years; BMI 23+/-2 kg/m(2)).. Plasma concentrations of PYY, GLP-1, PP and pro-NT were obtained.. PYY levels increased more in the RYGBP group than in the other groups after the test meal. GLP-1 levels rose in the RYGBP patients, with a small increase seen in the age-matched lean group. PP concentrations increased similarly in all groups postprandially. Pro-NT levels were highest in surgical patients, with no meal effect.. RYGBP subjects displayed exaggerated PYY and GLP-1 responses to a standardized meal and demonstrated higher pro-NT levels both pre- and postprandially. The findings indicate that possibly the alterations in gut peptide secretion may promote weight loss after gastric bypass surgery.

Topics: Adult; Bariatric Surgery; Cross-Sectional Studies; Eating; Fasting; Female; Glucagon-Like Peptide 1; Humans; Male; Neurotensin; Obesity, Morbid; Pancreatic Polypeptide; Peptide YY; Postprandial Period; Prospective Studies; Protein Precursors; Satiety Response; Weight Loss

To prospectively assess the relationship between circulating peptide YY (PYY), body weight, and glucose tolerance in severely obese subjects undergoing Roux-en-Y gastric bypass (RYGBP).. The mechanisms accounting for the beneficial effects of RYGBP on body weight and glucose homeostasis are not well understood.. Prospective study on the response of PYY to a standardized test meal (STM) and its relationship with weight loss and glucose homeostasis (fasting plasma glucose, HbA1c, HOMA-IR, HOMA-B) in nondiabetic (n = 25) and diabetic (n = 10) severely obese subjects evaluated before, and at 6 and 52 weeks after RYGBP.. The PYY response to a STM significantly increased (P < 0.001) already at 6 weeks at a time when subjects despite presenting a significant weight loss (-14.6% +/- 1.2%) were still markedly obese. Despite massive weight loss (-43.0% +/- 2.3%), no further increase in the area under the curve of PYY was observed at 52 weeks after surgery (P = 0.44). The PYY response to a STM at 6 weeks after surgery significantly correlated (r = 0.489, P < 0.05) with the percent excess weight loss at 32.5 +/- 1.1 months after surgery. In contrast, no significant correlation was found between PYY and glucose homeostasis parameters in nondiabetic and diabetic patients.. Our data support the hypothesis that an increased PYY response after meal ingestion is involved in the sustained weight loss observed after RYGBP. In contrast, our data does not support PYY being relevant in the changes in glucose homeostasis occurring after this type of bariatric surgery.

Topics: Adult; Biomarkers; Blood Glucose; Female; Follow-Up Studies; Gastric Bypass; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Male; Middle Aged; Obesity, Morbid; Peptide YY; Postoperative Period; Prospective Studies; Radioimmunoassay; Treatment Outcome; Weight Loss

Recent findings suggest that low plasma peptide YY (PYY) levels may contribute to diet-induced human obesity and justify PYY replacement therapy. Although the pharmacological value of PYY is controversial, further study of the secretion of the precursor PYY(1-36) and the pharmacologically active PYY(3-36) is indicated to determine the potential role in energy balance regulation.. Our objective was to determine the effects of acute and chronic changes in human body weight on circulating levels of the putative satiety hormone peptide YY.. Total plasma PYY levels (PYY(1-36) + PYY(3-36)) were measured in 66 lean, 18 anorectic, 63 obese, and 16 morbidly obese humans. In addition, total PYY was measured in 17 of the obese patients after weight loss and in the 18 anorectic patients after weight gain. Fasting PYY(3-36) levels were measured in 17 lean and 15 obese individuals.. Fasting total plasma PYY levels were highest in patients with anorexia nervosa (80.9 +/- 12.9 pg/ml, P < 0.05) compared with lean (52.4 +/- 4.6 pg/ml), obese (43.9 +/- 3.8 pg/ml), or morbidly obese (45.6 +/- 11.2 pg/ml) subjects. In obese patients, weight loss of 5.4% was associated with a 30% decrease in fasting total PYY plasma levels. In anorectic patients, weight gain had no effect on fasting PYY. PYY(3-36) levels did not differ between lean (96.2 +/- 8.6 pg/ml) and obese (91.5 +/- 6.9 pg/ml) subjects.. Our findings do not support a role for abnormal circulating PYY in human obesity. We conclude that circulating PYY levels in humans are significantly elevated in anorexia nervosa and, given the controversially discussed anorectic effect of PYY, could theoretically contribute to that syndrome.

Topics: Adult; Anorexia; Body Weight; Energy Intake; Fasting; Female; Humans; Leptin; Obesity, Morbid; Peptide Fragments; Peptide YY; Receptors, Cell Surface; Receptors, Leptin; Satiety Response; Weight Gain; Weight Loss

Surgically induced weight loss results in reduction of comorbidities in severely obese humans. Reversal of abnormal secretion of appetite-regulating gut hormones such as peptide YY (PYY) could be contributing to the improvement of cardiovascular risk factors.. Severely obese patients (n = 42, BMI = 45.7 +/- 5.3 kg/m(2)) underwent clinical examination and blood sampling for measurement of PYY, plasma lipids, oral glucose tolerance testing and assessment of insulin secretion (HOMA-%B) and action (HOMA-R, QUICKI) before and during 12 months following gastric banding. Comparisons were made at each time point of the study as well as across the total study period.. Weight loss after bariatric surgery resulted in improvement of insulin resistance by 54% (p < 0.03) and plasma triglycerides by 26% (p < 0.01) without changes in fasting PYY (16.2 +/- 8.7 pmol/l at baseline, 15.1 +/- 6.3 pmol/l at 12 months). Fasting PYY correlated negatively with plasma total cholesterol at baseline (p = 0.02) but was not associated with body weight, body mass or abdominal diameter. Individual changes in PYY (DeltaPYY) related to changes in insulin (Deltafasting insulin) at 12 months (r = -0.582, p = 0.02) and HOMA-B at 6 months (r = -0.677, p = 0.006) and 12 months (r = -0.660, p = 0.007). Diabetic status had no impact on these correlations.. PYY correlates with a major cardiovascular risk factor and surrogate parameters of insulin secretion but not to weight loss or body mass in severe obesity.

Topics: Adult; Analysis of Variance; Cardiovascular Diseases; Fasting; Female; Follow-Up Studies; Gastroplasty; Glucose; Glucose Tolerance Test; Humans; Insulin Resistance; Male; Middle Aged; Obesity, Morbid; Peptide YY; Risk Factors; Time Factors; Weight Loss

Circulating levels of the pancreatic beta-cell peptide hormone amylin and the gut peptide PYY[3-36] increase after nutrient ingestion. Both have been implicated as short-term signals of meal termination with anorexigenic and weight-reducing effects. However, their combined effects are unknown. We report that the combination of amylin and PYY[3-36] elicited greater anorexigenic and weight-reducing effects than either peptide alone. In high-fat-fed rats, a single ip injection of amylin (10 microg/kg) plus PYY[3-36] (1000 microg/kg) reduced food intake for 24 h (P < 0.05 vs. vehicle), whereas the anorexigenic effects of either PYY[3-36] or amylin alone began to diminish 6 h after injection. These anorexigenic effects were dissociable from changes in locomotor activity. Subcutaneous infusion of amylin plus PYY[3-36] for 14 d suppressed food intake and body weight to a greater extent than either agent alone in both rat and mouse diet-induced obesity (DIO) models (P < 0.05). In DIO-prone rats, 24-h metabolic rate was maintained despite weight loss, and amylin plus PYY[3-36] (but not monotherapy) increased 24-h fat oxidation (P < 0.05 vs. vehicle). Finally, a 4 x 3 factorial design was used to formally describe the interaction between amylin and PYY[3-36]. DIO-prone rats were treated with amylin (0, 4, 20, and 100 microg/kg.d) and PYY[3-36] (0, 200, 400 microg/kg.d) alone and in combination for 14 d. Statistical analyses revealed that food intake suppression with amylin plus PYY[3-36] treatment was synergistic, whereas body weight reduction was additive. Collectively, these observations highlight the importance of studying peptide hormones in combination and suggest that integrated neurohormonal approaches may hold promise as treatments for obesity.

Topics: Amyloid; Animals; Anti-Obesity Agents; Dietary Fats; Drug Synergism; Drug Therapy, Combination; Eating; Humans; Islet Amyloid Polypeptide; Male; Mice; Obesity; Peptide Fragments; Peptide YY; Rats; Weight Loss

Peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) are cosecreted in the same enteroendocrine L-cells of the gut and reported to inhibit food intake additively. However, findings in human studies regarding these peptides are controversial. The aim of this study was to analyze the relationships between fasting PYY, GLP-1, and weight status in morbidly obese patients before and after surgically induced weight loss.. Fasting GLP-1, PYY, glucose, and insulin concentrations; blood pressure; and body-mass index (BMI) were determined in 30 morbidly obese adults (mean BMI 45.8, mean age 40 years) before bariatric surgery [Roux-en-Y gastric bypass (RYGB): n = 19; gastric banding (GB): n = 11] and after weight loss (mean 50% excess weight loss) in the course of mean 2 years.. GLP-1 concentrations decreased (mean -20 pg/ml; mean -38%; p = 0.001) and PYY concentrations increased (mean +19 pg/ml; mean +19%, p = 0.036) after bariatric surgery. The weight loss and changes of GLP-1 were significantly (p < 0.05) more pronounced after RYGB as compared to GB, whereas the changes of PYY did not differ significantly between the patients who had undergone RYGB or GB.. In morbidly obese adults reducing their weight by bariatric surgery, fasting PYY levels increased and GLP-1 concentrations decreased independently of each other. Therefore, the relationship between PYY and GLP-1 seems more complicated than might be anticipated from animal and in vitro studies.

Topics: Adult; Blood Glucose; Blood Pressure; Body Mass Index; Enzyme-Linked Immunosorbent Assay; Female; Gastric Bypass; Gastroplasty; Glucagon-Like Peptide 1; Humans; Insulin; Male; Middle Aged; Obesity, Morbid; Peptide YY; Postoperative Period; Radioimmunoassay; Statistics, Nonparametric; Weight Loss

Polycystic ovary syndrome (PCOS) is a common condition associated with obesity and with reproductive and metabolic dysfunction. Abnormalities in appetite regulation in PCOS patients may contribute to difficulties in weight management.. We aimed to examine appetite, appetite hormones, and ad libitum food consumption before and after weight loss in overweight women with and without PCOS.. Overweight age- and weight-matched women with (n = 14) and without (n = 14) PCOS undertook an 8-wk energy-restricted diet (5185.3 +/- 141.6 kJ/d). At baseline and study end, subjects consumed a test meal (936 kJ; 25% of energy from protein, 9% from fat, and 67% from carbohydrate). Subjective appetite and circulating glucose, insulin, ghrelin, cholecystokinin, and peptide YY were assessed at 0, 15, 30, 45, 60, 90, 120, and 180 min. A mixed buffet lunch was then offered to assess ad libitum food intake.. Weight loss (4.2 +/- 3.9 kg) did not differ significantly between the 2 groups. Women with PCOS had significantly (P = 0.023) lower ghrelin concentrations before and after weight loss than did women without PCOS. The degree of postprandial ghrelin suppression was lower at weeks 0 (P = 0.048) and 8 (P = 0.069) in women with PCOS than in women without PCOS. There were no significant differences between the 2 groups in appetite responses, buffet consumption, or fasting or postprandial peptide YY and cholecystokinin before or after weight loss.. PCOS was associated with lower fasting ghrelin and a smaller postprandial ghrelin suppression both before and after weight loss but was not associated with other postprandial gut peptides, subjective satiety, or food intake. It is not clear whether appetite regulation is impaired in PCOS.

Topics: Adult; Appetite Regulation; Blood Glucose; Cholecystokinin; Eating; Female; Ghrelin; Homeostasis; Humans; Insulin; Motor Activity; Overweight; Peptide YY; Polycystic Ovary Syndrome; Postprandial Period; Weight Loss

Fermentable dietary fiber has been shown to cause fat loss and to increase peptide-YY (PYY) and glucagon-like peptide 1 (GLP-1) levels in rodents. In single meal tests, humans have an increase in PYY and GLP-1 to dietary fiber, but the response of these hormones to longer-term treatment is not known. Viscofiber (Cevena Bioproducts Inc., Edmonton, AB, Canada) is a high-viscosity fermentable dietary fiber made by a proprietary process from oats and barley. Seven healthy overweight and obese subjects were treated with a calorie-restricted diet, a lifestyle change program, and 4 g of Viscofiber/day for 16 weeks. Hunger, satiety, PYY, and GLP-1 were measured before and 1 hour after a standard meal test before and at week 14 of the study. Hunger and satiety were measured by Visual Analog Scales. PYY and GLP-1 were measured by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. Weight was reduced 3.07 +/- 3.13 kg (P < .05) over the 16 weeks. Fasting PYY increased 8.67 +/- 6.62 pg/mL (P < .05) and fasting GLP-1 increased 2.67 +/- 0.84 pmol/L (P < .01) at 14 weeks compared to baseline. Satiety increased 1.78 +/- 1.43 cm (P < .01) at the 1-hour post-meal time point on week 14 compared to the study baseline. We conclude that 14 weeks of treatment with Viscofiber at 4 g/day along with a lifestyle change program and diet causes weight loss and increases fasting PYY, fasting GLP-1, and satiety at 1 hour following a standard meal, which extends the single meal test observations in humans.

Topics: Adult; Dietary Fiber; Fasting; Female; Fermentation; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Peptide YY; Viscosity; Weight Loss

To study the effect of bariatric surgery on the entero-hypothalamic endocrine axis of humans and rodents.. Bariatric surgery is the most effective obesity treatment as it achieves substantial and sustained weight loss. Glycemic control and enhanced satiation improve before substantial weight loss occurs. Gut peptides, acting both peripherally and centrally, contribute to glycemic control and regulate food intake.. We examined meal-stimulated responses of insulin, ghrelin, peptide YY (PYY), glucagon-like-peptide-1 (GLP-1), and pancreatic polypeptide (PP) in humans and rodents following different bariatric surgical techniques.. Compared with lean and obese controls, patients following Roux-en-Y gastric bypass (RYGB) had increased postprandial plasma PYY and GLP-1 favoring enhanced satiety. Furthermore, RYGB patients had early and exaggerated insulin responses, potentially mediating improved glycemic control. None of these effects were observed in patients losing equivalent weight through gastric banding. Leptin, ghrelin, and PP were similar in both the surgical groups. Using a rodent model of jejuno-intestinal bypass (JIB), we showed elevated PYY and GLP-1 in JIB rats compared with sham-operated rats. Moreover, exogenous PYY reduced food intake and blockade of endogenous PYY increased food intake. Thus, higher plasma PYY following JIB may contribute to reduced food intake and contribute to weight loss.. Following RYGB and JIB, a pleiotropic endocrine response may contribute to the improved glycemic control, appetite reduction, and long-term changes in body weight.

Topics: Adult; Animals; Appetite; Bariatric Surgery; Cross-Sectional Studies; Female; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin; Male; Models, Animal; Obesity; Pancreatic Polypeptide; Peptide Hormones; Peptide YY; Rats; Rats, Wistar; Weight Loss

Topics: Adolescent; Anorexia Nervosa; Feeding Behavior; Female; Humans; Neuropeptide Y; Peptide YY; Weight Loss

Mechanisms that promote effective and sustained weight loss in persons who have undergone Roux-en-Y gastric bypass surgery are incompletely understood but may be mediated, in part, by changes in appetite. Peptide YY (PYY) is a gut-derived hormone with anorectic properties. We sought to determine whether gastric bypass surgery alters PYY levels or response to glucose.. PYY and ghrelin levels after a 75-gram oral glucose tolerance test were measured in 6 morbidly obese patients 1.5 +/- 0.7 (SE) years after gastric bypass compared with 5 lean and 12 obese controls.. After substantial body weight loss (36.8 +/- 3.6%) induced by gastric bypass, the PYY response to an oral glucose tolerance test was significantly higher than in controls (p = 0.01). PYY increased approximately 10-fold after a 75-gram glucose load to a peak of 303.0 +/- 37.0 pg/mL at 30 minutes (p = 0.03) and remained significantly higher than fasting levels for all subsequent time-points. In contrast, PYY levels in obese and lean controls increased to a peak of approximately 2-fold, which was only borderline significant. Ghrelin levels decreased in a symmetric but opposite fashion to that of PYY.. Gastric bypass results in a more robust PYY response to caloric intake, which, in conjunction with decreased ghrelin levels, may contribute to the sustained efficacy of this procedure. The findings provide further evidence for a role of gut-derived hormones in mediating appetite changes after gastric bypass and support further efforts to determine whether PYY(3-36) replacement could represent an effective therapy for obesity.

Topics: Anti-Obesity Agents; Appetite; Area Under Curve; Energy Intake; Female; Gastric Bypass; Ghrelin; Glucose Tolerance Test; Humans; Male; Obesity, Morbid; Peptide Hormones; Peptide YY; Weight Loss

To quantify plasma concentrations of hormones that regulate energy homeostasis in order to establish possible mechanisms for greater weight loss after Roux-en-Y gastric bypass (RYGBP) compared with gastric banding (BND).. Four groups of women were studied: lean (n = 8; mean BMI, 21.6 kg/m2); BND (n = 9; BMI, 35.8; 25% weight loss), RYGBP (n = 9; BMI, 34.2; 36% weight loss), and controls matched for BMI to the surgical groups (n = 11; BMI, 34.4).. Fasting total peptide YY (PYY) and PYY(3-36) immunoreactivity were similar among all groups, but the postprandial response in the RYGBP group was exaggerated, such that 30 minutes after the meal, total and PYY(3-36) levels were 2- to 4-fold greater compared with all other groups. Maximal postprandial suppression of total ghrelin was blunted in the BND group (13%) compared with RYGBP (27%). Postprandial suppression of octanoylated ghrelin was also less in BND (29%) compared with RYGBP (56%). Fasting insulin was lower in RYGBP (6.6 microU/mL) compared with BND (10.0 microU/mL). Compared with lean controls, leptin concentrations were significantly higher in BND but not in RYGBP. There was a greater increase in post-meal satiety in the RYGBP group compared with BND and overweight controls.. The differences between RYGBP and BND subjects in postprandial concentrations of PYY and ghrelin would be expected to promote increased satiety and earlier meal termination in RYGBP and may aid in greater weight loss. The differences in insulin and leptin concentrations associated with these procedures may also reflect differences in insulin sensitivity and energy partitioning.

Topics: Adult; Analysis of Variance; Area Under Curve; Female; Gastric Bypass; Gastroplasty; Ghrelin; Glucose Tolerance Test; Humans; Insulin; Leptin; Middle Aged; Obesity, Morbid; Peptide Hormones; Peptide YY; Postprandial Period; Satiety Response; Weight Loss

Bariatric surgeries, such as gastric bypass, result in dramatic and sustained weight loss that is usually attributed to a combination of gastric volume restriction and intestinal malabsorption. However, studies parceling out the contribution of enhanced intestinal stimulation in the absence of these two mechanisms have received little attention. Previous studies have demonstrated that patients who received intestinal bypass or Roux-en-Y surgery have increased release of gastrointestinal hormones. One possible mechanism for this increase is the rapid transit of nutrients into the intestine after eating. To determine whether there is increased secretion of anorectic peptides produced in the distal small intestine when this portion of the gut is given greater exposure to nutrients, we preformed ileal transpositions (IT) in rats. In this procedure, an isolated segment of ileum is transposed to the jejunum, resulting in an intestinal tract of normal length but an alteration in the normal distribution of endocrine cells along the gut. Rats with IT lost more weight (P < 0.05) and consumed less food (P < 0.05) than control rats with intestinal transections and reanastomosis without transposition. Weight loss in the IT rats was not due to malabsorption of nutrients. However, transposition of distal gut to a proximal location caused increased synthesis and release of the anorectic ileal hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY; P < 0.01). The association of weight loss with increased release of GLP-1 and PYY suggests that procedures that promote gastrointestinal endocrine function can reduce energy intake. These findings support the importance of evaluating the contribution of gastrointestinal hormones to the weight loss seen with bariatric surgery.

Topics: Adaptation, Physiological; Animals; Bariatrics; Energy Intake; Feeding Behavior; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptide 1; Ilium; Jejunum; Male; Peptide Fragments; Peptide YY; Protein Precursors; Rats; Rats, Long-Evans; Weight Loss

To help understand the mechanisms by which weight loss is maintained after Roux-en-Y gastric bypass (RYGBP), we measured circulating concentrations of total and bioactive octanoylated ghrelin, peptide YY (PYY), glucose, and insulin in the fasted state and in response to a liquid test meal in three groups of adult women: lean (n = 8); weight-stable 35 +/- 5 months after RYGBP (n = 12; mean body mass index, 33 kg/m(2)); and matched to the surgical group for body mass index and age (n = 12). Fasting plasma total ghrelin levels were nearly identical between RYGBP (425 +/- 54 pg/ml) and the matched controls (424 +/- 28 pg/ml) and highest in lean controls (564 +/- 103 pg/ml). The response to the test meal was comparable between lean and RYGBP groups, with 27% and 20% maximal suppression, respectively, whereas the magnitude of suppression was significantly diminished in the matched controls (17%) compared with the lean group. Fasting levels of octanoylated ghrelin were highest in the lean controls, 220 +/- 36 pg/ml vs. 143 +/- 27 in the RYGBP group (P = 0.05) and 127 +/- 12 pg/ml in the matched controls (P < 0.05). The magnitude of maximal postmeal suppression of octanoylated ghrelin was more marked than with total ghrelin, but similar among groups, ranging from 44-47%. In response to the test meal, there was an early exaggerated rise in PYY in the RYGBP group, such that the peak PYY concentration was 163 +/- 24 pg/ml compared with 58 +/- 17 (P < 0.01) and 77 +/- 23 (P < 0.05) in the matched and lean controls, respectively; area under the curve at 90 min was significantly greater compared with both control groups. Leptin and fasting insulin concentrations and homeostasis model of assessment insulin resistance indices were nearly identical between lean and RYGBP subjects and significantly higher in the body mass index-matched controls. In summary, the absence of a compensatory increase in ghrelin concentrations that usually occurs with diet-induced weight loss, and the exaggerated postprandial PYY response after RYGBP, may contribute to weight loss and to the ability of an individual to maintain weight loss after this surgical procedure.

Topics: Adult; Anastomosis, Roux-en-Y; Appetite; Blood Glucose; Fasting; Female; Gastric Bypass; Ghrelin; Humans; Insulin; Leptin; Pain Measurement; Peptide Hormones; Peptide YY; Weight Loss

Topics: Anastomosis, Roux-en-Y; Gastric Bypass; Ghrelin; Humans; Insulin; Peptide Hormones; Peptide YY; Weight Loss

The gut hormone peptide YY(3-36) (PYY) reduces food intake via hypothalamic Y2 receptors in the brain. There is not much known about PYY in obese children.. The objective of this study was to investigate the role of PYY in the metabolic changes in obese children and its change during weight loss.. The study was performed at a university medical center.. We studied 73 obese children and 45 age-matched normal-weight children.. We determined fasting serum total PYY and leptin by RIA in obese and normal-weight children. Fasting PYY was also measured in 28 obese children before and after completion of a 1-yr outpatient weight reduction program.. PYY, insulin, and body mass index were the main outcome measures.. Obese children demonstrated significantly lower PYY levels than lean children (median, 67 vs. 124 pg/ml; P < 0.001). Fasting PYY correlated negatively to the degree of overweight. PYY levels did not differ significantly between boys and girls, nor between prepubertal and pubertal children. The group of patients participating in the outpatient weight reduction program was divided into four quartiles according to their changes in body mass index SD score over a 1-yr period. PYY increased significantly in patients with the most effective weight loss, but decreased in the subgroup of children with weight gain.. PYY is negatively correlated to the degree of overweight, with reduced values in obese compared with normal-weight children. Decreased PYY levels could predispose subjects to develop obesity. Our results indicate that low pretreatment PYY levels that increase during weight loss may be a predictor of maintained weight loss.

Topics: Case-Control Studies; Child; Energy Metabolism; Fasting; Female; Homeostasis; Humans; Leptin; Male; Obesity; Peptide YY; Radioimmunoassay; Weight Loss

Peptide YY(3-36) [PYY(3-36)] is a hormone that is released after meal ingestion that is currently being investigated for the treatment of obesity; however, there are conflicting reports of the effects of PYY(3-36) on energy balance in rodent models. To shed light on this controversy, we studied the effect of PYY(3-36) on food intake and body weight in a nonhuman primate. Intravenous PYY(3-36) infusions before a morning meal transiently suppressed the rate of food intake but did not suppress the evening meal or 24-h intake. Twice-daily or continuous intravenous PYY(3-36) infusions to supraphysiological levels (levels that exceeded normal physiological levels) again suppressed the rate of feeding for the morning but not the evening meal. Twice-daily intravenous PYY(3-36) infusions for 2 weeks significantly decreased body weight in all test animals (average weight loss 1.9%) without changing insulin response to glucose infusion. These results show that endogenous PYY(3-36) may alter morning but not evening meal intake, and supraphysiological doses are required for effective suppression of food intake.

Topics: Animals; Drug Administration Schedule; Feeding Behavior; Glucose Tolerance Test; Macaca mulatta; Male; Peptide Fragments; Peptide YY; Time Factors; Weight Loss

Topics: Agouti-Related Protein; alpha-MSH; Animals; Anti-Obesity Agents; Appetite; Arcuate Nucleus of Hypothalamus; Ciliary Neurotrophic Factor; Clinical Trials as Topic; Cyclobutanes; Energy Intake; Ghrelin; Humans; Hunger; Intercellular Signaling Peptides and Proteins; Lactones; Leptin; Mice; Nerve Tissue Proteins; Neurons; Neuropeptide Y; Obesity; Orlistat; Peptide Fragments; Peptide Hormones; Peptide YY; Phentermine; Proteins; Receptors, Corticotropin; Receptors, Melanocortin; Weight Loss

The Peptide YY (PYY) secretion pattern was assessed in morbidly obese (MO) patients before and after vertical banded gastroplasty (VBG).. 12 MO patients (10 women, 2 men) age 29-62 years, BMI 50.7 +/- 9.6 kg/m2, treated with a VBG were studied. Before surgery, blood samples were taken in basal conditions of fasting and 10, 15, 20, 30 and 60 min after the ingestion of a semiliquid test meal. This was repeated in the same patients 6 and 12 months after VBG. Blood samples were also taken from 6 healthy non-obese subjects as controls. PYY plasma concentration was measured by radioimmunoassay with I125.. There were statistically significant differences between the preoperative PYY concentration in MO patients compared to controls. After a VBG, PYY concentration varied significantly compared to the preoperative levels. There was no significant difference between the PYY concentrations in the MO patients after VBG and the controls.. PYY concentration is lower in MO patients compared with non-obese. After VBG, PYY concentration gradually rises to the control levels.

Topics: Adult; Body Mass Index; Female; Gastroplasty; Humans; Male; Middle Aged; Obesity, Morbid; Peptide YY; Postoperative Period; Radioimmunoassay; Time Factors; Weight Loss

In the clinical setting, resection of the ileum results in an inferior functional outcome compared to jejunal resection. This may be related to a greater adaptive capacity of the ileum, intrinsic structural and functional differences, or regional differences in motor and hormonal function. Our aim was to evaluate the relative contributions of these factors to functional outcome after resection of the proximal or distal intestine. Twenty-four dogs underwent either intestinal transection or 50% resection of the proximal or distal intestine. Studies (nutritional status, absorption, adaptation, motility, peptide levels) were performed every four weeks until the animals were killed at 12 weeks. Caloric intake was similar in all four groups. Weight loss was greater and more sustained after distal resection (DR). Serum cholesterol levels decreased significantly only in the DR group. While stool weight and moisture were similar, the DR animals had persistent, significant steatorrhea. Intraluminal anaerobic bacteria and SCFA concentrations were significantly greater in the ileum but were not influenced by resection. Intestinal remnant length increased to a greater extent after proximal resection (PR), but circumference increased to a similar extent after both resections. Villus height and crypt depth increased significantly only after PR. MMC frequency was similar in all four groups. In the DR animals 26% of migrating motor complexes (MMCs) originated within the remnant. The jejunal remnant of these animals had a dominance of cluster activity similar to the intact distal ileum. Following PR, the postprandial motilin response was decreased. After DR, there were transient increases in neurotensin and PYY. Of the various factors evaluated, mucosal adaptation and the intestinal motor response appear most likely to explain the inferior nutritional and absorptive outcome associated with resection of the distal small intestine.

Topics: Adaptation, Physiological; Animals; Cholesterol; Dogs; Feces; Gastrointestinal Motility; Ileum; Intestinal Mucosa; Jejunum; Lipids; Methods; Motilin; Myoelectric Complex, Migrating; Neurotensin; Peptide YY; Weight Loss

Short day photoperiod promotes thermogenesis and extensive weight loss in Siberian hamsters (Phodopus sungorus sungorus). To determine whether a change in hormone-sensitive lipolysis occurs after short-photoperiod exposure, some lipolytic responses were measured on white adipocytes isolated from animals exposed in warm conditions to short or Long daylight photoperiod. The body mass of male Siberian hamsters exposed during 11 weeks to short days (SD; light: dark, 6:18 hr) reached only 50% of those kept in long days (LD; 16: 8 hr). In SD-hamsters, adipose depot mass also represented approximately 50% of the LD group. A lower DNA content was observed in intra-abdominal fat pads of SD-hamsters. Lipolytic responses to noradrenaline, adrenaline, isoproterenol and ACTH were unchanged. However, sensitivity to the beta-3 adrenergic agonist, BRL 37344, was moderately increased. The major component of the adrenergic control of lipolysis was mediated by beta-3 adrenoceptors in both LD- and SD-Siberian hamsters. The limited antilipolytic effect of alpha-2 adrenergic agonists, PYY or insulin was rather surprising in Siberian hamsters since these inhibitory systems are efficient in hibernants and other photoperiod-sensitive rodents. Our results show that, after short photoperiod exposure, white adipose tissue mass and DNA content are reduced, especially in the epididymal fat pad, with only minor changes in the adipocyte sensitivity to lipolytic hormones.

Topics: Adipocytes; Adipose Tissue; Adrenergic beta-Agonists; Adrenocorticotropic Hormone; Animals; Cricetinae; DNA; Epinephrine; Ethanolamines; Isoproterenol; Lipolysis; Male; Norepinephrine; Peptide YY; Phodopus; Photoperiod; Propanolamines; Sympathomimetics; Weight Gain; Weight Loss

The regulation of appetite and satiety is complex and may involve peptide mediators such as cholecystokinin (CCK) and neuropeptide Y (NPY). Studies have indicated that calories administered enterally and parenterally impact on feeding, and possibly via the release of such mediators. Recent data from our laboratory have shown that total parenteral nutrition (TPN) reduces sham feeding in dogs by 50%. We hypothesized that TPN may alter feeding via an NPY-mediated mechanism. To test our hypothesis, we examined the effect of continuous administration of TPN on NPY receptor levels in the rat brain. Rats were surgically prepared with intravenous catheters. After 72 h of TPN infusion, the rats were anesthesized with sodium pentobarbital and their brains were removed. Neuropeptide Y receptor density was assessed by autoradiography in the paraventricular nucleus, olfactory cortex, dentate gyrus, and thalamus. These results were compared to the control group receiving intravenous saline. A third group receiving enteral nutrition was examined as well. Neuropeptide Y receptor numbers were significantly increased in the paraventricular nucleus of rats receiving TPN compared to the groups receiving intravenous saline or enteral nutrition. We conclude that continuous parenteral nutrition significantly increases NPY receptor density in the rat brain suggesting that TPN may impact feeding via the regulation of NPY receptor-mediated effects.

Topics: Animals; Autoradiography; Blood Glucose; Brain Chemistry; Male; Paraventricular Hypothalamic Nucleus; Parenteral Nutrition, Total; Peptide YY; Radioligand Assay; Rats; Rats, Inbred F344; Receptors, Neuropeptide Y; Weight Loss

1. Plasma pancreatic polypeptide, plasma catecholamine, blood glucose, plasma insulin and plasma peptide YY concentrations were studied to assess differences between eight formerly obese and eight never-obese control women during 25 min of sham-feeding (with the sight and smell of an English breakfast) and for 5 h after they had ingested the meal (3514 kJ, 50% fat, 35% carbohydrate). The post-obese women had maintained their normal body weight for at least 3 months before the study. 2. The plasma noradrenaline concentration was not different between the groups either during fasting (post-obese women 0.08 +/- 0.01 ng/ml versus control women 0.10 +/- 0.01 ng/ml) or in the significant postprandial increase (P < 0.001). The plasma adrenaline concentration increased significantly during sham-feeding in the control group from 0.024 +/- 0.004 ng/ml to 0.033 +/- 0.004 ng/ml (P = 0.02) in contrast with the post-obese women, who had significantly lower plasma concentrations of adrenaline in the fasting state (post-obese 0.016 +/- 0.003 ng/ml versus control women 0.024 +/- 0.004 ng/ml, P = 0.003), during sham-feeding (post-obese women 0.018 +/- 0.002 ng/ml versus control women 0.033 +/- 0.004 ng/ml, P = 0.003) and in the postprandial increase (P = 0.003). The maximal postprandial response concentrations recorded 5 h after the meal were 0.025 +/- 0.003 ng/ml in post-obese women and 0.035 +/- 0.004 ng/ml in control subjects (P = 0.04). There were no significant differences in plasma pancreatic polypeptide, plasma peptide YY, plasma insulin, or blood glucose concentrations between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Glucose; Energy Intake; Epinephrine; Fasting; Female; Gastrointestinal Hormones; Humans; Insulin; Norepinephrine; Obesity; Pancreatic Polypeptide; Peptide YY; Peptides; Time Factors; Weight Loss