peptide-yy and Body-Weight

Despite greater health education, obesity remains one of the greatest health challenges currently facing the world. The prevalence of obesity among children and adolescents and the rising rates of prediabetes and diabetes are of particular concern. A deep understanding of regulatory pathways and development of new anti-obesity drugs with increased efficacy and safety are of utmost necessity. The 2 major biological players in the regulation of food intake are the gut and the brain as peptides released from the gut in response to meals convey information about the energy needs to brain centers of energy homeostasis. There is evidence that gut hormones not only pass the blood-brain barrier and bind to receptors located in different brain areas relevant for body weight regulation, but some are also expressed in the brain as part of hedonic and homeostatic pathways. Regarding obesity interventions, the only truly effective treatment for obesity is bariatric surgery, the long-term benefits of which may actually involve increased activity of gut hormones including peptide YY3-36 and glucagon-like peptide 1. This review discusses critical gut-hormones involved in the regulation of food intake and energy homeostasis and their effects on peripheral tissues versus central nervous system actions.

Topics: Body Weight; Brain; Eating; Energy Metabolism; Gastrointestinal Hormones; Gastrointestinal Tract; Glucagon-Like Peptide 1; Homeostasis; Humans; Pediatric Obesity; Peptide Fragments; Peptide YY

Obesity is one of the greatest public health challenges of the 21st century with 1.6 billion adults currently classified as being overweight and 400 million as obese. Obesity is causally associated with type 2 diabetes, hypertension, cardiovascular disease, obstructive sleep apnoea and certain forms of cancer and is now one of the leading causes of mortality and morbidity worldwide. The gastrointestinal tract is the largest endocrine organ in the body producing hormones that have important sensing and signaling roles in regulating body weight and energy expenditure. The last decade has witnessed a marked increase in our understanding of the role of gut hormones in energy homeostasis. Consequently, strategies aimed at modulating circulating gut hormone concentrations or targeting their receptors are being developed as potential pharmacotherapies for obesity. This review summarizes the current knowledge regarding the mechanisms, sites of action and effects of the anorectic gut hormones peptide tyrosine-tyrosine (PYY), pancreatic polypeptide (PP), oxyntomodulin, and amylin and of the unique orexigenic hormone, ghrelin.

Topics: Amyloid; Animals; Body Weight; Energy Metabolism; Gastrointestinal Hormones; Gastrointestinal Tract; Ghrelin; Homeostasis; Humans; Islet Amyloid Polypeptide; Obesity; Oxyntomodulin; Pancreatic Polypeptide; Peptide YY

Effective control of body weight and energy homeostasis requires stringent regulation of caloric intake and energy expenditure. Gut-brain interactions comprise a central axis for the control of energy homeostasis by integrating the intake of nutrients with an effective utilization of ingested calories either by storage or by expenditure as cellular fuel. Ghrelin, a stomach-derived peptide, is the only known circulating orexigenic hormone. It is acylated with a medium-chain fatty acid by the enzyme ghrelin O-acetyltransferase (GOAT) and displays a broad range of activity, from central control of food intake to peripheral functions such as gastric emptying and insulin secretion. PYY, a peptide produced by L cells of the small intestine and rectum, has been shown to inhibit gut motility and is proposed to stimulate a powerful central satiety response. In recent years, pharmacological studies in animals and clinical studies in humans have contributed to our knowledge of principal ghrelin and PYY actions. However, valuable findings from studies using ghrelin-deficient mice, ghrelin receptor [growth hormone secretagogue receptor-1a (GHSR1a)]-deficient mice, double-knockout mice (for ghrelin and GHSR), and GOAT-deficient or -overexpressor mice, as well as mice deficient for PYY or neuropeptide Y receptors have allowed better definition of the actual physiological functions of ghrelin and PYY. This review summarizes findings from mutant mouse studies with emphasis on respective gene knockout and transgenic animals and describes how these studies contribute to the current understanding of how endogenous ghrelin and PYY as two major representatives of endocrine gut-brain communications may regulate energy and glucose homeostasis.

Topics: Animals; Body Weight; Eating; Energy Metabolism; Ghrelin; Humans; Mice; Mice, Transgenic; Peptide YY

A variety of circulating signals provide essential information to the central nervous system (CNS) regarding nutritional status. The gastrointestinal system produces many such molecules that are now known to have profound effects on feeding behavior and the control of metabolism as a consequence of their ability to regulate the neural circuitry involved in metabolic homeostasis. Although many of these substances have been suggested to directly access such brain centers, their lipophobic characteristics suggest that alternative mechanisms should be considered. In this paper, we consider one such alternative, namely, that a specialized group of CNS structures collectively known as the sensory circumventricular organs (CVOs), which are not protected by the normal blood-brain barrier, may play important roles in such blood to brain communications. Specifically, we review a developing literature that shows receptors for, and functional actions of, gastrointestinal hormones such as amylin, cholecystokinin, ghrelin and peptide YY in the area postrema and subfornical organ. Collectively, these observations suggest potentially significant roles for the sensory CVOs in the regulation of energy balance.

Topics: Adipokines; Appetite Regulation; Area Postrema; Blood-Brain Barrier; Body Weight; Cholecystokinin; Energy Metabolism; Feeding Behavior; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Homeostasis; Humans; Neurons; Peptide Hormones; Peptide YY; Satiation; Signal Transduction; Subfornical Organ

The increasing prevalence of obesity and the associated morbidity and mortality has resulted in a major research effort to identify mechanisms that regulate appetite. It is well established that the hypothalamus and brain stem are major sites in the central nervous system (CNS) that regulate appetite. Until recently the missing element has been how information regarding food intake and energy stores is communicated to the CNS. Gut hormones have recently been found to be an important element in this regulation, communicating information regarding food intake to the CNS. Several gut hormones have been found to exert anorectic effects. These include members of the Pancreatic Polypeptide (PP)-fold family, namely PP itself and also peptide tyrosine-tyrosine (PYY), the first gut hormone shown to have appetite-inhibiting properties. The other main class of anorectic gut hormones are those derived by proteolytic processing from proglucagon, most importantly glucagon-like peptide-1 (GLP-1) and oxyntomodulin. All of these are currently being investigated as the basis of treatments to prevent the development of obesity. So far the only gastrointestinal hormone demonstrated to stimulate appetite is ghrelin. Potential sites and mechanisms of action and therapeutic use of these gastrointestinal hormones are discussed.

Topics: Animals; Appetite; Appetite Regulation; Body Weight; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Obesity; Oxyntomodulin; Pancreatic Polypeptide; Peptide YY; Proglucagon; Signal Transduction

The first hormone discovered in the gastrointestinal tract was secretin, isolated from duodenal mucosa. Some years later, two additional gastrointestinal hormones, gastrin and cholecystokinin (CCK), were discovered, but it was not until the 1970s that gastrointestinal endocrinology studies became more prevalent, resulting in the discovery of many more hormones. Here, we examine the role of gut hormones in energy balance regulation and their possible use as pharmaceutical targets for obesity.

Topics: Animals; Anti-Obesity Agents; Appetite Regulation; Body Weight; Energy Metabolism; Ghrelin; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Homeostasis; Humans; Obesity; Oxyntomodulin; Peptide Hormones; Peptide YY

Although the close link between body weight and fertility has been known for eons, only recently have the peripheral signals and neuroendocrine networks responsible for such a phenomenon begun to be identified. A key event in this field was the cloning of the adipocyte-derived hormone leptin, which has been demonstrated as a pivotal regulator for the integration of energy homeostasis and reproduction. In addition, other metabolic hormones, such as insulin, contribute to this physiological integration. Moreover, compelling experimental evidence implicates hormonal products of the gastrointestinal tract as adjuncts in the complex coordination and regulation of body weight and reproduction. Here, we review recent studies evaluating the reproductive effects and sites of action of ghrelin and PYY3-36, two hormonal signals of gastrointestinal origin involved in the control food intake and energy balance. In addition, we summarize the potential contribution of kisspeptin, the recently characterized gatekeeper of the GnRH system encoded by Kiss1 gene, to integrating reproductive function and energy status. Evidence suggests that besides having direct gonadal effects, ghrelin may participate in the regulation of gonadotropin secretion and it may influence the timing of puberty. Likewise, PYY3-36 modulates GnRH and gonadotropin release. In addition, the hypothalamic KiSS-1 system is sensitive to nutritional status, and its diminished expression during states of negative energy balance might contribute to the suppression of reproductive function in such conditions. We propose that the peripheral hormones, ghrelin and PYY3-36, and the central neuropeptide, kisspeptin, are 'novel' players in the neuroendocrine networks that integrate energy balance and reproduction.

Topics: Animals; Appetite Regulation; Body Weight; Energy Metabolism; Gastric Mucosa; Ghrelin; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Kisspeptins; Models, Biological; Peptide Fragments; Peptide Hormones; Peptide YY; Puberty; Reproduction; Signal Transduction; Tumor Suppressor Proteins

Energy balance is largely regulated by the central nervous system (CNS), which senses metabolic status from a wide range of humoral and neural signals, and controls energy intake. Accumulating evidence supports the model that stimulation of leptin- and ghrelin-responsive pathways, including the central melanocortin system, in the hypothalamus, contributes to the maintenance of body weight. Ghrelin is the brain-gut peptide with growth hormone-releasing and appetite-inducing activities. It is mainly secreted from the stomach and acts as an afferent signal to the hypothalamus and hindbrain. Leptin, the adipocyte hormone, is believed to tonically act as an afferent signal from adipose tissue to the brain, in particular hypothalamus, as a part of negative feedback loop regulating the size of energy stores and energy balance. Dysregulation of these pathways is a marker of changes in energy balance. Ghrelin is negatively correlated with weight and obese subjects have lower ghrelin levels than lean subjects, consistent with a compensatory rather than causal role for ghrelin in obesity. On the contrary, circulating leptin levels correlate in proportion to adiposity being high in obesity suggesting that human obesity is associated with insensitivity to leptin. The leptin resistance in diet-induced obesity emphasizes that environmental factors can modulate leptin sensitivity. It is speculated that through hypothalamic/pituitary axis ghrelin and leptin operate as a metabolic switch. Ghrelin actually transfers information from the stomach to the hypothalamus in cooperation with leptin and provides calories that growth hormone (GH) needs for growth and repair. Pharmacological manipulations of circulating hormone levels may work well in "cheating" the brain regarding information from the periphery. It might also be necessary to combine two or three agents to fight obesity. A combination of drugs that decrease preprandial appetite (ghrelin antagonist) and increase post-prandial satiety (gut hormone fragment peptide YY 3-36) might have a chance of achieving sustained weight loss. The administration of exogenous satiety hormone peptide YY 3-36 (PYY) may prevent the action of appetite-stimulating hypothalamic circuits on the anorexigenic melanocortin pathways.

Topics: Adipose Tissue; Animals; Appetite; Body Weight; Brain; Energy Metabolism; Ghrelin; Humans; Hypothalamus; Leptin; Obesity; Peptide Fragments; Peptide Hormones; Peptide YY; Pituitary Gland; Satiation; Signal Transduction

The significant burden of overweight and obesity on our society necessitates the development of lifestyle strategies that facilitate successful long-term body weight management. Recently, the discovery of novel cellular modulators of the brain-gut axis have generated much interest in possible therapeutic manipulation of these and other hormones that regulate energy intake. These modulators include the enterohormones ghrelin, peptide YY 3-36, and cholecystokinin, and the adipocyte-derived hormone leptin. There is some evidence that dietary macronutrient composition can influence concentrations of these hormones, which could impact sensations of hunger, satiety, and ultimately energy intake. The purpose of this review is to provide background information on these four peripheral hormones involved in energy intake regulation, to discuss what is currently known about their mechanism of action, and to present research findings related to the effect of macronutrient composition on concentrations and efficacy of these hormones. Potential applications of this information are also discussed.

Topics: Body Weight; Brain; Cholecystokinin; Eating; Energy Intake; Energy Metabolism; Feeding Behavior; Gene Expression Regulation; Ghrelin; Humans; Leptin; Peptide Fragments; Peptide Hormones; Peptide YY

The neuropeptide Y (NPY)/peptide YY (PYY) system has been implicated in the physiology of obesity for several decades. More recently ignited enormous interest in PYY3-36, an endogenous Y2-receptor agonist, as a promising anti-obesity compound. Despite this interest, there have been remarkably few subsequent reports reproducing or extending the initial findings, while at the same time studies finding no anti-obesity effects have surfaced. Out of 41 different rodent studies conducted (in 16 independent labs worldwide), 33 (83%) were unable to reproduce the reported effects and obtained no change or sometimes increased food intake, despite use of the same experimental conditions (i.e. adaptation protocols, routes of drug administration and doses, rodent strains, diets, drug vendors, light cycles, room temperatures). Among studies by authors in the original study, procedural caveats are reported under which positive effects may be obtained. Currently, data speak against a sustained decrease in food intake, body fat, or body weight gain following PYY3-36 administration and make the previously suggested role of the hypothalamic melanocortin system unlikely as is the existence of PYY deficiency in human obesity. We review the studies that are in the public domain which support or challenge PYY3-36 as a potential anti-obesity target.

Topics: Animals; Anti-Obesity Agents; Behavior, Animal; Body Weight; Data Interpretation, Statistical; Dipeptidyl Peptidase 4; Eating; Humans; Peptide Fragments; Peptide YY; Receptors, Neuropeptide Y; Satiety Response; Species Specificity; Stress, Physiological

The focus of this article is to review evidence that apolipoprotein A-IV (apo A-IV) acts as a satiety factor. Additionally, information regarding the general involvement of apo A-IV in the regulation of food intake and body weight is stated. Apo A-IV is a glycoprotein synthesized by the human intestine. In rodents, both the small intestine and liver secrete apo A-IV, but the small intestine is the major organ responsible for circulating apo A-IV. There is now solid evidence that the hypothalamus, especially the arcuate nucleus, is another active site of apo A-IV expression. Intestinal apo A-IV synthesis is markedly stimulated by fat absorption and does not appear to be mediated by the uptake or reesterification of fatty acids to form triglycerides. Rather, the local formation of chylomicrons acts as a signal for the induction of intestinal apo A-IV synthesis. Intestinal apo A-IV synthesis is also enhanced by a factor from the ileum, probably peptide tyrosine-tyrosine (PYY). The inhibition of food intake by apo A-IV is mediated centrally. The stimulation of intestinal synthesis and secretion of apo A-IV by lipid absorption are rapid; thus apo A-IV likely plays a role in the short-term regulation of food intake. Other evidence suggests that apo A-IV may also be involved in the long-term regulation of food intake and body weight, as it is regulated by both leptin and insulin. Chronic ingestion of a high-fat diet blunts the intestinal as well as the hypothalamic apo A-IV response to lipid feeding. It also suppresses apo A-IV gene expression in the hypothalamus. Whereas it is tempting to speculate that apo A-IV may play a role in diet-induced obesity, we believe the confirmation of such a proposal awaits further experimental evidence.

Topics: Animals; Apolipoproteins A; Body Weight; Eating; Gastrointestinal Tract; Humans; Infusions, Intravenous; Injections, Intraventricular; Peptide YY; Satiety Response

Obesity has reached epidemic levels in industrialized countries and is increasing worldwide. This trend has serious public health consequences, since obesity increases the risk of diabetes, hypertension, heart disease, sleep apnea, cancer, arthritis, cholelithiasis, fatty liver disease, and other complications. Obesity is the result of an imbalance between energy intake and expenditure; hence, an understanding of how gastrointestinal function is integrated with the hormonal regulation of energy balance is pertinent to the pathophysiology of obesity. Nutrients, peptides, and neural afferents from the gut influence the size and frequency of meals and satiety. The long-term regulation of energy stores is mediated primarily through the actions of adiposity hormones, such as leptin and insulin, in the hypothalamus and other neuronal circuits in the brain. Efforts are underway to determine how these peripheral and central pathways may be targeted for treatment of obesity and related diseases.

Topics: Animals; Appetite; Body Weight; Cholecystokinin; Energy Metabolism; Gastrointestinal Hormones; Ghrelin; Humans; Insulin; Leptin; Obesity; Peptide Hormones; Peptide YY; Peptides; Satiety Response; Stomach

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

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

Appetite and gastrointestinal hormones (GIHs) participate in energy homeostasis, feeding behavior and regulation of body weight. We demonstrated previously the superior effect of a hypocaloric diet regimen with lower meal frequency (B2) on body weight, hepatic fat content, insulin sensitivity and feelings of hunger compared to the same diet divided into six smaller meals a day (A6). Studies with isoenergetic diet regimens indicate that lower meal frequency should also have an effect on fasting and postprandial responses of GIHs. The aim of this secondary analysis was to explore the effect of two hypocaloric diet regimens on fasting levels of appetite and GIHs and on their postprandial responses after a standard meal. It was hypothesized that lower meal frequency in a reduced-energy regimen leading to greater body weight reduction and reduced hunger would be associated with decreased plasma concentrations of GIHs: gastric inhibitory peptide (GIP), glucagon-like peptide-1(GLP-1), peptide YY(PYY), pancreatic polypeptide (PP) and leptin and increased plasma concentration of ghrelin. The postprandial response of satiety hormones (GLP-1, PYY and PP) and postprandial suppression of ghrelin will be improved.. In a randomized crossover study, 54 patients suffering from type 2 diabetes (T2D) underwent both regimens. The concentrations of GLP-1, GIP, PP, PYY, amylin, leptin and ghrelin were determined using multiplex immunoanalyses.. Fasting leptin and GIP decreased in response to both regimens with no difference between the treatments (p = 0.37 and p = 0.83, respectively). Fasting ghrelin decreased in A6 and increased in B2 (with difference between regimens p = 0.023). Fasting PP increased in B2with no significant difference between regimens (p = 0.17). Neither GLP-1 nor PYY did change in either regimen. The decrease in body weight correlated negatively with changes in fasting ghrelin (r = -0.4, p<0.043) and the postprandial reduction of ghrelin correlated positively with its fasting level (r = 0.9, p<0.001). The postprandial responses of GIHs and appetite hormones were similar after both diet regimens.. Both hypocaloric diet regimens reduced fasting leptin and GIP and postprandial response of GIP comparably. The postprandial responses of GIHs and appetite hormones were similar after both diet regimens. Eating only breakfast and lunch increased fasting plasma ghrelin more than the same caloric restriction split into six meals. The changes in fasting ghrelin correlated negatively with the decrease in body weight. These results suggest that for type 2 diabetic patients on a hypocaloric diet, eating larger breakfast and lunch may be more efficient than six smaller meals during the day.

Topics: Adult; Aged; Body Weight; Caloric Restriction; Cross-Over Studies; Diabetes Mellitus, Type 2; Female; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon-Like Peptide 1; Humans; Hunger; Insulin Resistance; Leptin; Male; Meals; Middle Aged; Pancreatic Polypeptide; Peptide YY; Time Factors; Treatment Outcome

The effect of beverages commonly consumed by children in-between or with meals on short-term food intake (FI) and glycemic control has received little attention. Therefore, 2 experiments were conducted in 9- to 14-year-old children following a randomized repeated-measures design. Experiment 1 (n = 32) compared the effects of water (control) and isocaloric (130 kcal) amounts of 2% milk, chocolate milk, yogurt drink, and fruit punch on subjective appetite and FI. Experiment 2 (n = 20) compared the effects of isocaloric (130 kcal) amounts of 2% milk and fruit punch on subjective appetite, FI, and glycemic and appetite hormone responses. One serving of the beverages was given as a pre-meal drink at baseline (0 min) and a second serving 60 min later with an ad libitum pizza meal. Meal FI in experiment 1 was lower by 14% and 10%, respectively, after chocolate milk and yogurt drink (p < 0.001), but not milk, compared with water. Cumulative energy intake (beverages plus meal) was higher after caloric beverages than water. In experiment 2, no differences occurred in pre-meal but post-meal glucose was 83% higher in overweight/obese than normal-weight children (p = 0.02). Milk led to higher pre-meal glucagon-like peptide-1 and post-meal peptide tyrosine tyrosine (PYY) than fruit punch (p < 0.01) but insulin did not differ between treatments. In conclusion, dairy products consumed before and with a meal have more favourable effects on FI, appetite, and satiety hormones than a sugar-sweetened beverage, but all caloric beverages result in more cumulative calories than if water is the beverage.

Topics: Adolescent; Appetite; Blood Glucose; Body Mass Index; Body Weight; Child; Dairy Products; Dietary Carbohydrates; Dietary Proteins; Eating; Energy Intake; Female; Fruit and Vegetable Juices; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin; Male; Meals; Nutritive Sweeteners; Peptide YY; Satiation

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

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

Whey protein (WP), when consumed in small amounts prior to a meal, improves post-meal glycemic control more than can be explained by insulin-dependent mechanisms alone. The objective of the study was to identify the mechanism of action of WP beyond insulin on the reduction of post-meal glycemia. In a randomized crossover study, healthy young men received preloads (300 ml) of WP (10 and 20 g), glucose (10 and 20 g) or water (control). Paracetamol (1.5 g) was added to the preloads to measure gastric emptying. Plasma concentrations of paracetamol, glucose, and β-cell and gastrointestinal hormones were measured before preloads (baseline) and at intervals before (0-30 min) and after (50-230 min) a preset pizza meal (12 kcal/kg). Whey protein slowed pre-meal gastric emptying rate compared to the control and 10 g glucose (P<.0001), and induced lower pre-meal insulin and C-peptide than the glucose preloads (P<.0001). Glucose, but not WP, increased pre-meal plasma glucose concentrations (P<.0001). Both WP and glucose reduced post-meal glycemia (P=.0006) and resulted in similar CCK, amylin, ghrelin and GIP responses (P<.05). However, compared with glucose, WP resulted in higher post-meal GLP-1 and peptide tyrosine-tyrosine (PYY) and lower insulin concentrations, without altering insulin secretion and extraction rates. For the total duration of this study (0-230 min), WP resulted in lower mean plasma glucose, insulin and C-peptide, but higher GLP-1 and PYY concentrations than the glucose preloads. In conclusion, pre-meal consumption of WP lowers post-meal glycemia by both insulin-dependent and insulin-independent mechanisms.

Topics: Adolescent; Adult; Blood Glucose; Body Mass Index; Body Weight; C-Peptide; Cholecystokinin; Cross-Over Studies; Gastric Emptying; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Glucagon-Like Peptide 1; Humans; Insulin; Islet Amyloid Polypeptide; Male; Milk Proteins; Peptide YY; Whey Proteins; Young Adult

To investigate the effect of nutrient stimulation of gut hormones by oligofructose supplementation on appetite, energy intake (EI), body weight (BW) and adiposity in overweight and obese volunteers.. In a parallel, single-blind and placebo-controlled study, 22 healthy overweight and obese volunteers were randomly allocated to receive 30 g day(-1) oligofructose or cellulose for 6 weeks following a 2-week run-in. Subjective appetite and side effect scores, breath hydrogen, serum short chain fatty acids (SCFAs), plasma gut hormones, glucose and insulin concentrations, EI, BW and adiposity were quantified at baseline and post-supplementation.. Oligofructose increased breath hydrogen (P < 0.0001), late acetate concentrations (P = 0.024), tended to increase total area under the curve (tAUC)420 mins peptide YY (PYY) (P = 0.056) and reduced tAUC450 mins hunger (P = 0.034) and motivation to eat (P = 0.013) when compared with cellulose. However, there was no significant difference between the groups in other parameters although within group analyses showed an increase in glucagon-like peptide 1 (GLP-1) (P = 0.006) in the cellulose group and a decrease in EI during ad libitum meal in both groups.. Oligofructose increased plasma PYY concentrations and suppressed appetite, while cellulose increased GLP-1 concentrations. EI decreased in both groups. However, these positive effects did not translate into changes in BW or adiposity.

Topics: Adiposity; Adult; Appetite; Appetite Regulation; Area Under Curve; Blood Glucose; Body Weight; Cellulose; Dietary Fiber; Dietary Supplements; Energy Intake; Fatty Acids; Female; Glucagon-Like Peptide 1; Healthy Volunteers; Humans; Insulin; Male; Middle Aged; Obesity; Oligosaccharides; Overweight; Patient Compliance; Peptide YY; Single-Blind Method; Young Adult

Our aim was to examine the effects of GLP-1 and PYY3-36, separately and in combination, on energy intake, energy expenditure, appetite sensations, glucose and fat metabolism, ghrelin, and vital signs in healthy overweight men. Twenty-five healthy male subjects participated in this randomized, double-blinded, placebo-controlled, four-arm crossover study (BMI 29 ± 3 kg/m(2), age 33 ± 9 yr). On separate days they received a 150-min intravenous infusion of 1) 0.8 pmol·kg(-1)·min(-1) PYY3-36, 2) 1.0 pmol·kg(-1)·min(-1) GLP-1, 3) GLP-1 + PYY3-36, or 4) placebo. Ad libitum energy intake was assessed during the final 30 min. Measurements of appetite sensations, energy expenditure and fat oxidation, vital signs, and blood variables were collected throughout the infusion period. No effect on energy intake was found after monoinfusions of PYY3-36 (-4.2 ± 4.8%, P = 0.8) or GLP-1 (-3.0 ± 4.5%, P = 0.9). However, the coinfusion reduced energy intake compared with placebo (-30.4 ± 6.5%, P < 0.0001) and more than the sum of the monoinfusions (P < 0.001), demonstrating a synergistic effect. Coinfusion slightly increased sensation of nausea (P < 0.05), but this effect could not explain the effect on energy intake. A decrease in plasma ghrelin was found after all treatments compared with placebo (all P < 0.05); however, infusions of GLP-1 + PYY3-36 resulted in an additional decrease compared with the monoinfusions (both P < 0.01). We conclude that coinfusion of GLP-1 and PYY3-36 exerted a synergistic effect on energy intake. The satiating effect of the meal was enhanced by GLP-1 and PYY3-36 in combination compared with placebo. Coinfusion was accompanied by slightly increased nausea and a decrease in plasma ghrelin, but neither of these factors could explain the reduction in energy intake.

Topics: Adolescent; Adult; Anthropometry; Appetite; Blood Glucose; Body Weight; Cross-Over Studies; Double-Blind Method; Energy Intake; Energy Metabolism; Fatty Acids, Nonesterified; Food Preferences; Ghrelin; Glucagon-Like Peptide 1; Humans; Infusions, Intravenous; Insulin; Male; Middle Aged; Nausea; Overweight; Peptide Fragments; Peptide YY; Postprandial Period; Taste

Increased delivery of bile acid salts (BA) to distal L-cells and altered TGR5 receptor activation may contribute to the early and substantial increases in gut peptide secretion seen after bariatric surgery. To further elucidate a potential role of BA in the secretion of GLP-1 and PYY, we analyzed plasma BA concentrations in 14 morbidly obese patients undergoing gastric bypass or sleeve gastrectomy in a prospective, randomized 1-year trial.. Patients received a standard test meal and blood was collected before and after eating, prior to, and 1 week, 3 months, and 12 months after surgery.. Pre-surgery, basal BA concentrations were significantly lower in bariatric patients than in healthy controls. One year post-surgery, bariatric patients expressed variably increased BA concentrations (gastric bypass patients ∼2 fold increase, P ≤ 0.05). However, whereas in both patient groups, marked increases in GLP-1 and PYY and improved glycemic control was seen already 1 week and 3 months post-surgery, changes in plasma BA followed a different pattern: basal and postprandial plasma BA concentrations increased much slower, more progressively with significant increases only 1-year post-surgery.. Based on these findings, BA do not appear to be key mediators of the early increase in GLP-1 and PYY response in post-bariatric patients.

Topics: Adult; Bile Acids and Salts; Blood Glucose; Body Mass Index; Body Weight; Gastrectomy; Gastric Bypass; Glucagon-Like Peptide 1; Humans; Obesity, Morbid; Peptide YY; Pilot Projects; Postprandial Period; Prospective Studies

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

Retraining obese adolescents to eat more slowly will lead to beneficial changes in circulating concentrations of gastrointestinal satiety hormones.. Ghrelin and peptide tyrosine-tyrosine were measured during an oral glucose tolerance test, at baseline and at 12 months during a randomized trial assessing the clinical effectiveness of a device (Mandometer) designed to retrain eating behavior. This computerized scale provided real-time feedback during meals in the intervention arm (n = 14) to slow down the speed of eating. The control group (n = 13) received only standard care aimed at improving lifestyle behavior. The Mandometer elicited greater improvements in weight loss than standard care.. Compared with baseline, only those using the Mandometer exhibited lower mean levels of fasting ghrelin (48.14 ± 18.47 vs. 68.45 ± 17.78 pg/ml; P = 0.002) and mean ghrelin area under the curve (72.08 ± 24.11 vs. 125.50 ± 29.72 pg/ml × min; P < 0.001) at 12 months. Absolute mean suppression in ghrelin at 60 min was enhanced (-40.50 ± 21.06 vs. -12.14 ± 19.74 pg/ml × min; P = 0.001). Peptide tyrosine-tyrosine response at 90 min remained unaltered in the standard care arm, whereas those in the Mandometer arm increased (P < 0.001): the mean 90-min response increased by 72 pg/ml [95% confidence interval (CI) 52-92 pg/ml] between baseline and 12 months. In a partial correlation analysis adjusting for change (Δ) in body mass index sd scores, Δ meal duration correlated negatively with Δ absolute suppression in ghrelin at 60 min (r = -0.58; P = 0.037; 95% CI -0.79 to -0.27) and Δ ghrelin area under the curve (r = -0.62; P = 0.025; 95% CI -0.81 to -0.31).. Retraining obese adolescents to eat more slowly has a significant impact on the gastrointestinal hormone response to a carbohydrate load, suggesting that externally modifiable eating behaviors actually regulate the hormonal response to food.

Topics: Adolescent; Body Weight; Child; Equipment and Supplies; Feeding Behavior; Female; Gastrointestinal Hormones; Ghrelin; Health; Humans; Life Style; Male; Obesity; Peptide YY; Treatment Outcome; Weight Reduction Programs

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

Roux-en-Y gastric bypass (gastric bypass) patients reportedly have changes in perception and consumption of sweet-tasting foods. This study aimed to further investigate alterations in sweet food intake in rats and sucrose detection in humans after gastric bypass. Wistar rats were randomized to gastric bypass or sham-operations and preference for sucrose (sweet), sodium chloride (salty), citric acid (sour) and quinine hydrochloride (bitter) was assessed with standard two-bottle intake tests (vs. water). Intestinal T1R2 and T1R3 expression and plasma levels of glucagon-like-peptide 1 (GLP-1) and peptide YY (PYY) were measured. Furthermore, obese patients and normal weight controls were tested for sucrose taste detection thresholds pre- and postoperatively. Visual analogue scales measuring hedonic perception were used to determine the sucrose concentration considered by patients and controls as "just about right" pre- and postoperatively. Gastric bypass reduced the sucrose intake relative to water in rats (p<0.001). Preoperative sucrose exposure reduced this effect. Preference or aversion for compounds representative of other taste qualities in naïve rats remained unaffected. Intestinal T1R2 and T1R3 expression was significantly decreased in the alimentary limb while plasma levels of GLP-1 and PYY were elevated after bypass in rats (p=0.01). Bypass patients showed increased taste sensitivity to low sucrose concentrations compared with controls (p<0.05), but both groups considered the same sucrose concentration as "just about right" postoperatively. In conclusion, gastric bypass reduces sucrose intake relative to water in sucrose-naïve rats, but preoperative sucrose experience attenuates this effect. Changes in sucrose taste detection do not predict hedonic taste ratings of sucrose in bypass patients which remain unchanged. Thus, factors other than the unconditional affective value of the taste may also play a role in determining food preferences after gastric bypass.

Topics: Analysis of Variance; Animals; Body Weight; Choice Behavior; Dose-Response Relationship, Drug; Drinking; Eating; Energy Intake; Female; Food Preferences; Gastric Bypass; Gene Expression Regulation; Glucagon-Like Peptide 1; Humans; Intestine, Small; Male; Obesity; Pain Measurement; Peptide YY; Rats; Rats, Wistar; Receptors, G-Protein-Coupled; RNA, Messenger; Sucrose; Sweetening Agents; Taste; Taste Threshold; Time Factors

Obesity is a major public health issue worldwide. Understanding how the brain controls appetite offers promising inroads toward new therapies for obesity. Peptide YY (PYY) and glucagon-like peptide 1 (GLP-1) are coreleased postprandially and reduce appetite and inhibit food intake when administered to humans. However, the effects of GLP-1 and the ways in which PYY and GLP-1 act together to modulate brain activity in humans are unknown. Here, we have used functional MRI to determine these effects in healthy, normal-weight human subjects and compared them to those seen physiologically following a meal. We provide a demonstration that the combined administration of PYY(3-36) and GLP-1(7-36 amide) to fasted human subjects leads to similar reductions in subsequent energy intake and brain activity, as observed physiologically following feeding.

Topics: Adult; Appetite; Body Weight; Brain; Eating; Energy Intake; Fasting; Female; Glucagon-Like Peptide 1; Humans; Immunoassay; Infusions, Intravenous; Magnetic Resonance Imaging; Male; Obesity; Peptide Fragments; Peptide YY; Postprandial Period; Single-Blind Method

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

To evaluate the impact of gradual weight loss and the positive effect of sibutramine on metabolic parameters and the levels of serotonin and neuropeptide YY3-36 levels in patients with exogenous constitutional obesity (ECO).. The study included 36 patients (24 women and 12 men; mean age 37.56 +/- 0.9 years) with a verified diagnosis of ECO. The height, body weight, waist and hip circumference (WC and HC), and body mass index (BMI) were determined. Adipose tissue content was estimated by a bioimpedance method using an adipose mass analyzer. Serum peptide YY3-36 levels were measured by enzyme immunoassay and blood serotonin concentrations were estimated by high performance liquid chromatography with an electrochemical method.. 12-week sibutramine therapy caused a significant reduction in body weight, WC, HC, and BMI (p < 0.05) in all the patients. At the same time they were found to have a considerable body composition change (total body and visceral fat was decreased, total body water increased, and systemic metabolism was lowered). The mean peptide YY3-36 level was significantly decreased. Sibutramine did not affect the serum content of total serotonin in the sera of patients.. Sibutramine used in the combined therapy in patients with ECO contributes to an effective and steady-state weight loss. Sibutramine treatment causes a reduction in total neuropeptide YY3-36, systemic metabolism, and adipose tissue at the expense of the visceral depot.

Topics: Adult; Anthropometry; Appetite Depressants; Body Composition; Body Weight; Combined Modality Therapy; Cyclobutanes; Female; Humans; Male; Obesity; Peptide Fragments; Peptide YY; Serotonin; Treatment Outcome

The objective of this study was to identify mechanisms through which valproic acid (VPA) causes weight gain. Healthy participants (N = 52) were randomized to VPA or placebo in a double-blind study. Energy intake (EI) was measured in the laboratory at lunch and dinner, and physical activity (PA) was measured with accelerometry. Glucose levels and hormones [Peptide YY(3-36), glucagon-like peptide-1 (GLP-1), leptin, ghrelin, insulin] that regulate EI were measured. Assessments occurred at baseline and week 3. Change from baseline was evaluated with mixed models (alpha = 0.05). Weight significantly increased in the VPA group (+0.49 kg), but not the placebo group. The VPA group increased fast food fats cravings and decreased glucose levels compared with placebo. Change in weight, EI and PA did not differ by group. Within group analyses indicated that the VPA group increased PA, hunger, binge eating, depression and GLP-1. VPA-associated weight gain is not likely due to changes in PA or the gut hormones studied. Although EI did not increase when measured after 3 weeks of treatment, VPA decreased glucose levels and increased motivation to eat; hence, EI might have increased in the short-term. Research testing VPA on short-term (1 week) EI, metabolism, and substrate partitioning is warranted.

Topics: Adolescent; Adult; Anticonvulsants; Attitude; Blood Glucose; Body Weight; Creatinine; Delayed-Action Preparations; Eating; Feeding Behavior; Female; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin; Leptin; Lipids; Male; Middle Aged; Motor Activity; Patient Compliance; Peptide Fragments; Peptide YY; Serum Albumin; Valproic Acid

We aimed to test the effects of three different weight maintenance diets on appetite, glucose and fat metabolism following an initial low-energy diet (LED) induced body weight loss. Following an 8-week LED and a 2-3-week refeeding period, 131 subjects were randomized to three diets for 6 months: MUFA, moderate-fat (35-45 energy percentage (E%) fat), high in MUFA with low glycaemic index; LF, low fat (20-30 E% fat) or CTR, control (35 E% fat). A meal test study was performed in a subgroup, before and after the 6-month dietary intervention, with forty-two subjects completing both meal tests. No difference in body weight, energy intake or appetite ratings were observed between diets. Both the LF and MUFA diets compared to CTR diet reduced postprandial glycaemia and insulinaemia and lowered fasting insulin from month 0 to month 6. Following the 8-week LED period lower levels of the appetite regulating peptides, pancreatic polypeptide, peptide YY, glucagon-like peptide-1 and glucagon-like peptide-2, along with increased appetite scores were seen in comparison to measurements performed after the 6-month dietary intervention. In conclusion, the two competing diets, MUFA and LF, were equally good with respect to glucose metabolism, whereas the CTR diet resembling the typical Western diet, high in SFA, sugar and high glycaemic carbohydrates, indicated associations to lowering of insulin sensitivity. Lower levels of appetite regulatory peptides along with increased appetite scores following an 8-week LED and 2-3-week refeeding period, suggest that strategies for physiological appetite control following a LED period are needed, in order to prevent weight regain.

Topics: Adult; Analysis of Variance; Appetite Regulation; Area Under Curve; Blood Glucose; Body Mass Index; Body Weight; Diet, Fat-Restricted; Energy Intake; Fatty Acids, Monounsaturated; Female; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Glycemic Index; Humans; Insulin; Male; Obesity; Pancreatic Polypeptide; Peptide YY; Time Factors; Triglycerides

Carbohydrate-restricted diets (CRDs) have been shown to reduce body weight, whereas whole egg intake has been associated with increased satiety. The purpose of this study was to evaluate the effects of additional dietary cholesterol and protein provided by whole eggs while following a CRD on insulin resistance and appetite hormones. Using a randomized blind parallel design, subjects were allocated to an egg (640 mg/d additional dietary cholesterol) or placebo (0 mg/d additional dietary cholesterol) group for 12 weeks while following a CRD. There were significant reductions in fasting insulin (P < .025) and fasting leptin concentrations (P < .01) for both groups, which were correlated with the reductions in body weight and body fat (P < .05 and P < .01, respectively). Both groups reduced insulin resistance as measured by the homeostatic model assessment of insulin resistance (P < .025). There was a significant decrease in serum glucose levels observed after the intervention. We did not observe the expected increases in plasma ghrelin levels associated with weight loss, suggesting a mechanism by which subjects do not increase appetite with CRD. To confirm these results, the subjective measures of satiety using visual analog scale showed that both groups felt more "full" (P < .05), "satisfied" (P < .001), and "wanted to eat less" (P < .001) after the intervention. These results indicate that inclusion of eggs in the diet (additional dietary cholesterol) did not modify the multiple beneficial effects of CRD on insulin resistance and appetite hormones.

Topics: Adult; Aged; Analysis of Variance; Appetite; Blood Glucose; Body Composition; Body Weight; Cholesterol, Dietary; Diet, Carbohydrate-Restricted; Diet, Reducing; Dietary Proteins; Eggs; Energy Intake; Ghrelin; Hormones; Humans; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Pancreatic Polypeptide; Peptide YY; Satiation

Ghrelin and peptide YY (PYY) are both hormones derived from the gastrointestinal tract involved in appetite regulation. The cholinergic part of the vagal nerve is involved in the regulation of glucose and insulin. The aim of this study was to examine the effects of the cholinergic antagonist atropine on ghrelin, PYY, glucose, and insulin under basal conditions and after meal ingestion in lean and obese subjects.. Eight lean and eight obese subjects were included in a randomized, double-blind, placebo-controlled crossover study with 4 study days in randomized order (atropine/placebo +/- breakfast). Plasma ghrelin, PYY, insulin, and glucose were measured. Hunger and satiety feelings were rated on a 10-cm visual analog scale.. In lean individuals, atropine led to a decrease in ghrelin concentrations comparable and nonadditive with breakfast ingestion and a significant decrease in both basal and meal-induced PYY concentrations. In obese subjects, atropine did not significantly change ghrelin or PYY concentrations, whereas it induced a comparable increase in heart rate and meal-induced glucose concentrations in the two study groups. Only lean, not obese, subjects experienced sustained feelings of satiety after breakfast.. The impaired cholinergic regulation of the postprandial drop in ghrelin concentrations and rise in PYY concentrations might be part of the deregulated food intake in obese subjects.

Topics: Adult; Atropine; Blood Glucose; Body Weight; Cholinergic Fibers; Cross-Over Studies; Eating; Female; Gastrointestinal Tract; Ghrelin; Heart Rate; Humans; Insulin; Insulin Resistance; Male; Obesity; Parasympatholytics; Peptide YY; Postprandial Period; Satiety Response; Vagus Nerve

Ghrelin is secreted primarily by the stomach and circulates as both acylated and desacyl ghrelin. Acylated (but not desacyl) ghrelin stimulates appetite. Both concentrations are elevated in Prader-Willi syndrome (PWS), suggesting that ghrelin may contribute to hyperphagia and overweight in these subjects. We evaluated whether long-acting octreotide (Oct) decreases acylated and desacyl ghrelin concentrations, body mass, appetite and compulsive behaviour towards food in adolescents with PWS.. A 56-week prospective, randomized, cross-over trial.. Nine subjects with PWS (age 14.6 (10.8-18.9) years, body mass index (BMI) Z-score +1.9 (0.6-3.0)) received either Oct (30 mg) or saline i.m. every 4 weeks for 16 weeks and were switched over to the other treatment after a 24-week washout period.. Eight subjects completed the study. Oct caused a decrease in both acylated (-53%) and desacyl (-54%) fasting ghrelin concentrations (P<0.05) but did not significantly affect BMI. Oct had no significant effect on peptide YY concentrations, appetite or compulsive behaviour towards food. Oct caused a decrease in insulin-like growth factor-I concentrations, an increase in HbA1c and transient elevation of blood glucose in two subjects. Three subjects developed gallstones.. Oct treatment caused a prolonged decrease in ghrelin concentrations in adolescents with PWS but did not improve body mass or appetite. Future intervention studies aiming at clarifying the role of ghrelin in PWS should focus on the administration of specific inhibitors of ghrelin secretion or ghrelin receptor activity that do not interfere with other appetite-regulating peptides.

Topics: Adolescent; Appetite; Blood Glucose; Body Composition; Body Height; Body Mass Index; Body Weight; Child; Cross-Over Studies; Feeding Behavior; Female; Gallbladder Diseases; Gastrointestinal Agents; Ghrelin; Homeostasis; Humans; Insulin-Like Growth Factor I; Male; Octreotide; Peptide YY; Prader-Willi Syndrome; Ultrasonography

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

Peptide YY (PYY) is released from the distal small intestine and colon after meals and reduces appetite by increasing satiety. The amount of PYY released is proportional to calories ingested. Fat ingestion has also been reported to stimulate PYY release.. The objective of the study was to determine whether macronutrient composition influences postprandial serum PYY levels by comparing 1 wk of a weight-maintenance low-carbohydrate, high-fat (LCHF) diet with a low-fat, high-carbohydrate (LFHC) diet.. In this randomized crossover study, 18 obese subjects (14 females, 4 males, mean body mass index 35.6 +/- 2.9 kg/m(2)) were randomly assigned initially to 1 wk of a weight-maintenance LCHF or LFHC diet, after which a test meal of identical composition was given and serum PYY levels were assessed for 2.5 h postprandially. After a 1-wk washout period, subjects were crossed over and retested.. After 1 wk, mean postprandial area under the curve PYY after the LCHF test meal was 1.5-fold greater than after the LFHC test meal (P < 0.001). The LCHF diet led to 55% higher levels of postprandial serum PYY levels, compared with the LFHC diet (P = 0.005).. These data show that a LCHF diet stimulates PYY secretion more than a LFHC diet in obese individuals.

Topics: Adiponectin; Adult; Blood Glucose; Body Weight; Cross-Over Studies; Diet, Carbohydrate-Restricted; Diet, Fat-Restricted; Dietary Carbohydrates; Dietary Fats; Energy Intake; Female; Homeostasis; Humans; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; Peptide YY; Postprandial Period

Soy isoflavones show structural and functional similarities to estradiol. Available data indicate that estradiol and estradiol-like components may interact with gut "satiety hormones" such as peptide YY (PYY) and ghrelin, and thus influence body weight. In a randomized, double-blind, placebo-controlled, cross-over trial with 34 healthy postmenopausal women (59 +/- 6 years, BMI: 24.7 +/- 2.8 kg/m2), isoflavone-enriched cereal bars (50 mg isoflavones/day; genistein to daidzein ratio 2:1) or non-isoflavone-enriched control bars were consumed for 8 weeks (wash-out period: 8-weeks). Seventeen of the subjects were classified as equol producers. Plasma concentrations of ghrelin and PYY, as well as energy intake and body weight were measured at baseline and after four and eight weeks of each intervention arm.. Body weight increased in both treatment periods (isoflavone: 0.40 +/- 0.94 kg, P < 0.001; placebo: 0.66 +/- 0.87 kg, P = 0.018), with no significant difference between treatments. No significant differences in energy intake were observed (P = 0.634). PYY significantly increased during isoflavone treatment (51 +/- 2 pmol/L vs. 55 +/- 2 pmol/L), but not during placebo (52 +/- 3 pmol/L vs. 50 +/- 2 pmol/L), (P = 0.010 for treatment differences, independent of equol production). Baseline plasma ghrelin was significantly lower in equol producers (110 +/- 16 pmol/L) than in equol non-producers (162 +/- 17 pmol/L; P = 0.025).. Soy isoflavone supplementation for eight weeks did not significantly reduce energy intake or body weight, even though plasma PYY increased during isoflavone treatment. Ghrelin remained unaffected by isoflavone treatment. A larger and more rigorous appetite experiment might detect smaller differences in energy intake after isoflavone consumption. However, the results of the present study do not indicate that increased PYY has a major role in the regulation of body weight, at least in healthy postmenopausal women.

Topics: Aged; Body Weight; Cross-Over Studies; Double-Blind Method; Fasting; Female; Ghrelin; Humans; Isoflavones; Middle Aged; Peptide Hormones; Peptide YY; Postmenopause; Soy Foods

The gut hormone peptide YY (PYY) belongs to the pancreatic polypeptide (PP) family along with PP and neuropeptide Y (NPY). These peptides mediate their effects through the NPY receptors of which there are several subtypes (Y1, Y2, Y4, and Y5). The L cells of the gastrointestinal tract are the major source of PYY, which exists in two endogenous forms: PYY(1-36) and PYY(3-36). The latter is produced by the action of the enzyme dipeptidyl peptidase-IV (DPP-IV). PYY(1-36) binds to and activates at least three Y receptor subtypes (Y1, Y2, and Y5), whereas PYY(3-36) is more selective for Y2 receptor (Y2R). The hypothalamic arcuate nucleus, a key brain area regulating appetite, has access to nutrients and hormones within the peripheral circulation. NPY neurons within the arcuate nucleus express the Y2R. In response to food ingestion plasma PYY(3-36) concentrations rise within 15 min and plateau by approximately 90 min. The peak PYY(3-36) level achieved is proportional to the calories ingested, suggesting that PYY(3-36) may signal food ingestion from the gut to appetite-regulating circuits within the brain. We found that peripheral administration of PYY(3-36) inhibited food intake in rodents and increased C-Fos immunoreactivity in the arcuate nucleus. Moreover, direct intra-arcuate administration of PYY(3-36) inhibited food intake. We have shown that Y2R null mice are resistant to the anorectic effects of peripherally administered PYY(3-36), suggesting that PYY(3-36) inhibits food intake through the Y2R. In humans, peripheral infusion of PYY(3-36), at a dose which produced normal postprandial concentrations, significantly decreased appetite and reduced food intake by 33% over 24 h. These findings suggest that PYY(3-36) released in response to a meal acts via the Y2R in the arcuate nucleus to physiologically regulate food intake.

Topics: Adult; Animals; Appetite Regulation; Arcuate Nucleus of Hypothalamus; Body Weight; Cross-Over Studies; Digestive System Physiological Phenomena; Double-Blind Method; Eating; Feeding Behavior; Female; Humans; Male; Mice; Peptide YY; Rats; Receptors, Neuropeptide Y

TOTUM-63, a fibre and polyphenol rich plant-based composition, has been demonstrated to significantly improve body weight and glucose homeostasis in animal models of obesity. Our study aimed at exploring whether the mechanisms include modulation of gut (glucose-dependent insulinotropic peptide (GIP), glucagon-like petide-1 (GLP-1), cholecystokinin (CCK), peptide YY (PYY)) and pancreatic (insulin, glucagon) hormones, all important regulators of glucose control, appetite and body weight.. Male C57BL/6JRJ mice were assigned to either standard chow (CON), high fat diet (HF, 60% energy from fat) or HF-TOTUM-63 (HF diet 60% supplemented with TOTUM-63 2.7%) for 10 weeks. In vivo glucose homeostasis (oral glucose tolerance test (OGTT), intraperitoneal pyruvate tolerance test (ipPTT)), glucose-induced portal vein hormone concentration, gut hormone gene expression and protein content as well as enteroendocrine cell contents were assessed at the end of the dietary intervention. The present study evidenced that TOTUM-63 reduced food intake, limited weight gain and improved glucose and pyruvate tolerance of HF-fed animals. This was associated with an increase in PYY content in the colon, an altered pattern of PYY secretion between fasted and glucose-stimulated states, and with a significant improvement in the portal vein concentration of GLP-1, insulin and glucagon, but not GIP and CCK, in response to glucose stimulation.. Overall, these data suggest that TOTUM-63 might have a specific impact on gut L-cells and on the expression and secretion of GLP-1 and PYY incretins, potentially contributing to the reduced food intake, body weight gain and improved glucose homeostasis.

Topics: Animals; Blood Glucose; Body Weight; Diet, High-Fat; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Humans; Insulin; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Peptide YY; Plant Extracts; Polyphenols; Pyruvates; Weight Gain

The hypothalamus is an important brain region for the regulation of energy balance. Roux-en-Y gastric bypass (RYGB) surgery and gut hormone-based treatments are known to reduce body weight, but their effects on hypothalamic gene expression and signaling pathways are poorly studied.. Diet-induced obese male Wistar rats were randomized into the following groups: RYGB, sham operation, sham + body weight-matched (BWM) to the RYGB group, osmotic minipump delivering PYY3-36 (0.1 mg/kg/day), liraglutide s.c. (0.4 mg/kg/day), PYY3-36 + liraglutide, and saline. All groups (except BWM) were kept on a free choice of high- and low-fat diets. Four weeks after interventions, hypothalami were collected for RNA sequencing.. While rats in the RYGB, BWM, and PYY3-36 + liraglutide groups had comparable reductions in body weight, only RYGB and BWM treatment had a major impact on hypothalamic gene expression. In these groups, hypothalamic leptin receptor expression as well as the JAK-STAT, PI3K-Akt, and AMPK signaling pathways were upregulated. No significant changes could be detected in PYY3-36 + liraglutide-, liraglutide-, and PYY-treated groups.. Despite causing similar body weight changes compared to RYGB and BWM, PYY3-36 + liraglutide treatment does not impact hypothalamic gene expression. Whether this striking difference is favorable or unfavorable to metabolic health in the long term requires further investigation.

Topics: Animals; Body Weight; Caloric Restriction; Disease Models, Animal; Energy Metabolism; Gastric Bypass; Gastrointestinal Hormones; Gene Expression; Hypothalamus; Liraglutide; Male; Obesity; Peptide Fragments; Peptide YY; Rats; Rats, Wistar; Signal Transduction; Transcriptome

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

Consuming a diet high in prebiotic fiber has been associated with improved metabolic and gut microbial parameters intergenerationally, although studies have been limited to maternal intake with no studies examining this effect in a paternal model.. Male Sprague Dawley rats were allocated to either (1) control or (2) oligofructose-supplemented diet for nine weeks and then mated. Offspring consumed control diet until 16 weeks of age. Bodyweight, body composition, glycemia, hepatic triglycerides, gastrointestinal hormones, and gut microbiota composition were measured in fathers and offspring.. Paternal energy intake was reduced, while satiety inducing peptide tyrosine tyrosine (PYY) gut hormone was increased in prebiotic versus control fathers. Increased serum PYY persisted in female prebiotic adult offspring. Hepatic triglycerides were decreased in prebiotic fathers with a similar trend (. Although paternal prebiotic intake before conception improves metabolic and microbiota outcomes in fathers, effects on offspring were limited with increased serum satiety hormone levels and changes to only select gut bacteria.

Topics: Animals; Blood Glucose; Body Composition; Body Weight; Dietary Supplements; Fathers; Fatty Acids, Volatile; Female; Gastrointestinal Hormones; Gastrointestinal Microbiome; Homeostasis; Male; Oligosaccharides; Peptide YY; Prebiotics; Rats; Rats, Sprague-Dawley; RNA, Ribosomal, 16S; Triglycerides

We explored the effect of carboxymethylated wheat bran dietary fibers (DFs) on mice with type 2 diabetes (T2D) (induced by HFD combined with STZ) and their possible hypoglycemic mechanism. After feeding the diabetic mice with modified DFs for four weeks, the DFs had lipid lowering and anti-hyperglycemic effect, via increasing the levels of insulin, GLP-1, PYY, and SCFAs in diabetic mice, and improving the histopathology of liver and pancreas. qRT-PCR results showed that the intake of DFs up-regulated the expression levels of G6Pase and Prkce, and down regulated the expression levels of Glut2 and InsR in the liver of diabetic mice. It is suggested that DFs may play a role by inhibiting 1,2-DAG-PKCε pathway, improving insulin receptor activity and insulin signal transduction. 16 S rDNA high-throughput sequencing results showed that the DFs significantly improved the relative abundance of Akkermansia muciniphila, increased the diversity of gut microbiota and reduced the ratio of Firmicutes to Bacteroidetes, thus promoting the hypoglycemic and hypolipidemic effect on diabetic mice. Our study can foster the further understanding of the gut modulatory biomarkers and related metabolites, and may extend the basis for DFs as a potential dietary intervention to prevent or treat the T2D.

Topics: Animals; Body Weight; Diabetes Mellitus, Experimental; Dietary Fiber; Fatty Acids, Volatile; Gastrointestinal Microbiome; Gene Expression; Glucagon-Like Peptide 1; Hypoglycemic Agents; Hypolipidemic Agents; Liver; Male; Mice, Inbred C57BL; Pancreas; Peptide YY; Streptozocin; Triticum

The objective of this research was to evaluate activation of the ileal brake in broiler chickens using diets containing semi-purified wheat (WS; rapidly and highly digested) and pea (PS; slowly and poorly digested) starch. Diets were formulated to contain six WS:PS ratios (100:0, 80:20, 60:40, 40:60, 20:80, 0:100) and each starch ratio was fed to 236 Ross 308 male broilers housed in 4 litter floor pens. At 28 d of age, the effect of PS concentration was assessed on starch digestion, digestive tract morphology, and digesta pH and short-chain fatty acid (SCFA) concentration. Glucagon-like peptide-1 (GLP-1) and peptide tyrosine-tyrosine (PYY) status were assessed in serum (ELISA) and via gene expression in jejunal and ileal tissue (proglucagon for GLP-1). Data were analyzed using regression analyses, and significance was accepted at P ≤ 0.05. Increasing dietary PS resulted in reduced starch digestibility in the small intestine, but had no effect in the colon. Crop content pH responded quadratically to PS level with an estimated minimum at 55% PS. Total SCFA increased linearly in the crop with PS level, but changed in a quadratic fashion in the ileum (estimated maximum at 62% PS). Ceacal SCFA concentrations were highest for the 80 and 100% PS levels. The relative empty weight (crop, small intestine, colon), length (small intestine) and content (crop jejunum, Ileum) of digestive tract sections increased linearly with increasing PS concentration. Dietary treatment did not affect serum GLP-1 or PYY or small intestine transcript abundance. In conclusion, feeding PS increased the presence of L-cell activators (starch, SCFA) and increased trophic development and content of the digestive tract, suggestive of L-cell activation. However, no direct evidence of ileal brake activation was found by measuring venous blood levels of GLP-1 or PYY or corresponding gene expression in small intestine tissue.

Topics: Animal Nutritional Physiological Phenomena; Animals; Body Weight; Chickens; Digestion; Fatty Acids, Volatile; Glucagon-Like Peptide 1; Ileum; Male; Peptide YY; Starch

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

Bariatric surgery results in increased intestinal secretion of hormones GLP-1 and anorexigenic PYY, which is believed to contribute to the clinical efficacy associated with the procedure. This observation raises the question whether combination treatment with gut hormone analogs might recapitulate the efficacy and mitigate the significant risks associated with surgery. Despite PYY demonstrating excellent efficacy and safety profiles with regard to food intake reduction, weight loss, and glucose control in preclinical animal models, PYY-based therapeutic development remains challenging given a low serum stability and half-life for the native peptide. Here, combined peptide stapling and PEG-fatty acid conjugation affords potent PYY analogs with >14 h rat half-lives, which are expected to translate into a human half-life suitable for once-weekly dosing. Excellent efficacy in glucose control, food intake reduction, and weight loss for lead candidate

Topics: Amino Acid Sequence; Animals; Body Weight; Drug Interactions; Eating; Engineering; Glucagon-Like Peptide-1 Receptor; Half-Life; Models, Molecular; Obesity; Peptide YY; Polyethylene Glycols; Protein Conformation; Rats; Receptors, Neuropeptide Y

Combination therapies of anorectic gut hormones partially mimic the beneficial effects of bariatric surgery. Thus far, the effects of a combined chronic systemic administration of Glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine 3-36 (PYY. High-fat diet (HFD)-induced obese male Wistar rats were randomized into six treatment groups: (1) RYGB, (2) sham-operation (shams), (3) liraglutide, (4) PYY. RYGB reduced food intake and achieved sustained weight loss. Combined PYY. Liraglutide and PYY

Topics: Animals; Body Weight; Combined Modality Therapy; Diet, High-Fat; Eating; Food Preferences; Gastric Bypass; Hypoglycemic Agents; Liraglutide; Male; Obesity; Peptide YY; Rats; Rats, Wistar

The aim of the present study was to assess the effect of the PYY3-36, as a potential therapy for the type 2 diabetes mellitus (T2DM), induced by high fat diet (HFD) and an intraperitoneal (i.p.) administration of streptozotocin (STZ) in albino rats.. Forty adult male albino Wistar rats were divided into: 1) control group (C, in which the rats were fed with a standard diet and received vehicle; 2) diabetic group (D, in which T2DM was induced by feeding the rats with HFD for four weeks followed by a single i.p. injection of 35 mg/kg STZ, this group was also allowed to have HFD till the end of the study; and 3) D+PYY3-36 group (in which the diabetic rats were treated with 50 µg/kg i.p. PYY3-36 twice a day for one week). Food intake, water intake, body weight (b.w.), visceral fat weight (VFW), liver glycogen content, serum levels of glucose, insulin, and interleukin-6 (IL-6), were measured. Homeostatic-model assessment of insulin resistance (HOMA-IR) was estimated. The gene expression of the hypothalamic neuropeptide Y (NPY) and visceral nuclear factor kappa B (NF-κB) were assessed by a reverse transcription polymerase chain reaction (RT-PCR).. The PYY3-36 administration to the diabetic group of rats significantly increased the serum insulin levels and liver glycogen content, decreased the body weight, VFW, food intake, water intake, serum levels of the glucose, IL-6, and HOMA-IR. It also decreased the expression of both the hypothalamic NPY and the visceral fat NF-κB.. With respect to the fact of improved insulin release and enhanced insulin sensitivity (an effect that may be mediated via suppressing accumulation of visceral fat and inflammatory markers), in the rats treated with PYY3-36, the PYY3-36 might be considered for the future as a promising therapeutic tool in T2DM.

Topics: Adiposity; Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Drinking; Eating; Insulin Resistance; Intra-Abdominal Fat; Male; Organ Size; Peptide Fragments; Peptide YY; Rats; Rats, Wistar; Receptors, Neuropeptide Y; Streptozocin

Peptide YY(3-36) ((PYY(3-36)) and glucagon like peptide 1 (GLP-1) in combination reduce food intake and body weight in an additive or synergistic manner in animal models and in humans. Nevertheless, the mechanisms behind are not completely understood. The present study aims to investigate the effect of combining PYY(3-36) and the GLP-1 receptor agonist exendin-4 (Ex4) by examining acute food intake and global neuronal activation as measured by c-fos in C57BL/6 J mice. An additive reduction in food intake was found 1.5 h after s.c dosing with the combination of PYY(3-36) (200 μg/kg) and Ex4 (2.5 μg/kg). This was associated with a synergistic enhancement of c-fos reactivity in central amygdalar nucleus (CeA), rostral part of the mediobasal arcuate nucleus (ARH), supratrigeminal nucleus (SUT), lateral parabrachial nucleus (PB), area postrema (AP) and nucleus tractus solitarius (NTS) compared to vehicle, PYY(3-36) and Ex4 individually dosed mice. The regions activated by Ex4 individually and PYY(3-36) and Ex4 in combination resembled each other, but the combination group had a significantly stronger c-fos response. Twenty-five brain areas were activated by PYY(3-36) and Ex4 in combination compared to vehicle versus nine brain areas by Ex4 individually. No significant increase in c-fos reactivity was found by PYY(3-36) compared to vehicle dosed mice. The neuronal activation of ARH and the AP/NTS to PB to CeA pathway is important for appetite regulation while SUT has not previously been reported in the regulation of energy balance. As PYY(3-36) and Ex4 act on different neurons leading to recruitment of different signalling pathways within and to the brain, an interaction of these pathways may contribute to their additive/synergistic action. Thus, PYY(3-36) boosts the effect of Ex4 possibly by inducing less inhibition of neuronal activity leading to an enhanced neuronal activity induced by Ex4.

Topics: Amygdala; Animals; Body Weight; Eating; Exenatide; Hypothalamus; Mice; Neurons; Peptide Fragments; Peptide YY; Proto-Oncogene Proteins c-fos

The objective of this study is to examine the effect of maternal and weaning intact protein- and amino acid-based diets on regulation of food intake, intake regulatory hormones, and body weight in dams and their male offspring. Pregnant Wistar rats were allocated to two groups (

Topics: Animals; Blood Glucose; Body Weight; Eating; Female; Ghrelin; Insulin; Male; Maternal Nutritional Physiological Phenomena; Peptide YY; Pregnancy; Rats; Rats, Wistar; Weaning

Understanding the mechanisms underlying the remarkable beneficial effects of gastric bypass surgery is important for the development of non-surgical therapies or less invasive surgeries in the fight against obesity and metabolic disease. Although the intestinal L-cell hormones glucagon-like peptide-1 (GLP-1) and peptide tyrosine-tyrosine (PYY) have attracted the most attention, direct tests in humans and rodents with pharmacological blockade or genetic deletion of either the GLP1-receptor (GLP1R) or the Y2-receptor (Y2R) were unable to confirm their critical roles in the beneficial effects gastric bypass surgery on body weight and glucose homeostasis. However, new awareness of the power of combinatorial therapies in the treatment of metabolic disease would suggest that combined blockade of more than one signaling pathway may be necessary to reverse the beneficial effects of bariatric surgery.. The metabolic effects of high-fat diet and the ability of Roux-en-Y gastric bypass surgery to lower food intake and body weight, as well as improve glucose handling, was tested in GLP1R and Y2R-double knockout (GLP1RKO/Y2RKO) and C57BL6J wildtype (WT) mice.. GLP1RKO/Y2RKO and WT mice responded similarly for up to 20 weeks on high-fat diet and 16 weeks after RYGB. There were no significant differences in loss of body and liver weight, fat mass, reduced food intake, relative increase in energy expenditure, improved fasting insulin, glucose tolerance, and insulin tolerance between WT and GLP1RKO/Y2RKO mice after RYGB.. Combined loss of GLP1R and Y2R-signaling was not able to negate or attenuate the beneficial effects of RYGB on body weight and glucose homeostasis in mice, suggesting that a larger number of signaling pathways is involved or that the critical pathway has not yet been identified.

Topics: Animals; Bariatric Surgery; Blood Glucose; Body Weight; Diet, High-Fat; Energy Metabolism; Gastric Bypass; Gene Expression Regulation; Glucagon-Like Peptide-1 Receptor; Insulin; Insulin Resistance; Male; Metabolic Diseases; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Peptide YY; Receptors, G-Protein-Coupled; Transcriptome

Dairy proteins-whey protein, in particular-are satiating and often recommended for weight control; however, little is known about the mechanisms by which whey protein and its components promote satiety and weight loss. We used diet-induced obese rats to determine whether the hypophagic effects of diets that are enriched with whey and its fractions, lactalbumin and lactoferrin, are mediated by the gut hormone, peptide YY (PYY). We demonstrate that high protein diets that contain whey, lactalbumin, and lactoferrin decreased food intake and body weight with a concurrent increase in PYY mRNA abundance in the colon and/or plasma PYY concentrations. Of importance, blockade of PYY neuropeptide Y receptor subtype 2 (Y2) receptors with a peripherally restricted antagonist attenuated the hypophagic effects of diets that are enriched with whey protein fractions. Diets that are enriched with whey fractions were less preferred; however, in a modified conditioned taste preference test, PYY Y2 receptor blockade induced hyperphagia of a lactoferrin diet, but caused a reduction in preference for Y2 antagonist-paired flavor, which suggested that PYY signaling is important for lactoferrin-induced satiety, but not essential for preference for lactoferrin-enriched diets. Taken together, these data provide evidence that the satiety of diets that are enriched with whey protein components is mediated, in part, via enhanced PYY secretion and action in obese male rats.-Zapata, R. C., Singh, A., Chelikani, P. K. Peptide YY mediates the satiety effects of diets enriched with whey protein fractions in male rats.

Topics: Animals; Body Weight; Eating; Feeding Behavior; Hyperphagia; Male; Peptide YY; Rats; Receptors, Gastrointestinal Hormone; Safety; Whey Proteins

Apathy is observed across several neurological and psychiatric conditions; however, its pathogenesis remains unclear. We clarified the involvement of brain-gut signaling in the disruption of goal-directed behavior. Male C57BL/6J mice were exposed to water immersion (WI) stress for 3 days. Food intake and nesting behavior were measured as indexes of motivation. Repeated WI caused decrease in food intake and nesting behavior. Plasma levels of peptide YY (PYY), IL-6, and ratio of dopamine metabolites in the striatum were significantly elevated after WI. PYY and IL-6 administration significantly decreased nesting behavior. The reductions in feeding and nesting behavior were blocked by PYY receptor (Y2R) antagonist or dopamine agonist. The ameliorative effect of the Y2R antagonist was diminished by the dopamine D2 receptor (D2R) antagonist. The reduction in goal-directed behavior is associated with dysfunction of D2R signaling via increased peripheral PYY, suggesting that PYY antagonism is a novel candidate for decline of motivation in several depressive diseases.

Topics: Animals; Apathy; Behavior, Animal; Body Weight; Corticosterone; Dopamine; Eating; Gene Expression Regulation; Humans; Hypothalamus; Immersion; Interleukin-6; Male; Mice, Inbred C57BL; Models, Biological; Nesting Behavior; Organ Size; Peptide YY; Receptors, Dopamine D2; Receptors, Neuropeptide Y; Water

Non-starch polysaccharides (NSP) present in wheat and barley can act as anti-nutrients leading to an increase in digesta viscosity and a reduction in nutrient digestibility. Xylanase, an NSP-degrading enzyme, has been shown to increase nutrient digestibility in pigs. The objectives of this study were: (1) to identify the optimum inclusion level of xylanase in grower pig diets by measuring the effect of increasing enzyme levels on growth performance, the concentration of volatile fatty acids (VFA) and peptide YY concentration in portal and peripheral blood of grower pigs and (2) to increase our understanding of the interrelationships between xylanase inclusion, VFA production and peptide YY secretion. A total of 512 grower pigs ((Large White×Landrace)×MAXGRO) were allocated to pens creating 32 replicates of four pigs per pen per treatment. Pigs were allocated to trial weighing 14.2±0.31 kg and remained on trial until ~41.5±3.31 kg. The experiment was a dose response design with four inclusion levels (0, 8000, 16 000 or 32 000 BXU/kg) of xylanase (Econase XT). Diets were cereal-based wheat, barley mix formulated to meet or exceed the nutrient requirements of grower pigs. Body weight and feed intake were recorded to calculate growth performance. Pen faecal samples were collected to estimate DM, organic matter (OM) and crude fibre (CF) apparent total-tract digestibility. At the end of the trial 16 pigs per treatment were euthanised by schedule 1 procedures. Peripheral and portal blood samples were collected for peptide YY and VFA analysis. The addition of xylanase to the diet had no effect on growth performance, DM, OM or CF total-tract digestibility; however, xylanase tended to have a quadratic effect on ileum pH with higher pH values recorded for pigs fed a diet supplemented with 8000 and 16 000 BXU/kg xylanase (P<0.1). Xylanase had no effect on peptide YY levels or VFA concentration. Total VFA concentration was higher in portal compared with peripheral blood (P<0.05). In conclusion, the addition of xylanase had no effect on grower pig performance, nutrient digestibility, VFA concentration or peptide YY concentration when fed up to 32 000 BXU/kg over a 35-day period. Pig performance was good for all treatments throughout the trial suggesting that diet quality was sufficient thus there were no beneficial effects of adding xylanase.

Topics: Animal Feed; Animals; Body Weight; Diet; Dietary Supplements; Digestion; Edible Grain; Endo-1,4-beta Xylanases; Fatty Acids, Volatile; Feces; Female; Gastrointestinal Tract; Hordeum; Male; Peptide YY; Random Allocation; Swine; Triticum

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

Peptide YY 3-36 (PYY3-36) is known as a critical satiety factor that reduces food intake both in rodents and humans. Although the anorexic effect of PYY3-36 is assumed to be mediated mainly by the Y2 receptor, the involvement of other Y-receptors in this process has never been conclusively resolved. Amongst them, the Y5 receptor (Y5R) is the most likely candidate to also be a target for PYY3-36, which is considered to counteract the anorectic effects of Y2R activation. In the present study, we show that short-term treatment of diet-induced obese wild-type (WT) and Y5R knockout mice (Y5KO) with PYY3-36 leads to a significantly reduced food intake in both genotypes, which is more pronounced in Y5R KO mice. Interestingly, chronic PYY3-36 infusion via minipumps to WT mice causes an increased cumulative food intake, which is associated with increased body weight gain. By contrast, lack of Y5R reversed this effect. Consistent with the observed increased body weight and fat mass in WT-treated mice, glucose tolerance was also impaired by chronic PYY3-36 treatment. Again, this was less affected in Y5KO mice, suggestive of a role of Y5R in the regulation of glucose homeostasis. Taken together, our data suggest that PYY3-36 mediated signalling via Y5 receptors may counteract the anorectic effects that it mediates via the Y2 receptor (Y2R), consequently lowering bodyweight in the absence of Y5 signalling. These findings open the potential of combination therapy using PYY3-36 and Y5R antagonists to enhance the food intake reducing effects of PYY3-36.

Topics: Animals; Anorexia; Body Weight; Bone and Bones; Diet, High-Fat; Eating; Glucose; Homeostasis; Mice, Knockout; Obesity; Peptide Fragments; Peptide YY; Receptors, Neuropeptide Y

To investigate factors causing diabetes recurrence after sleeve gastrectomy (SG) and duodenal-jejunal bypass (DJB).. SG and DJB were performed on rats with diabetes induced by high-fat diet (HFD) and streptozotocin (STZ). HFD was used to induce diabetes recurrence at 4 wk postoperatively. Body weight, oral glucose tolerance test, homeostatic model assessment of insulin resistance (HOMA-IR), insulin signaling [IR, insulin receptor substrate (IRS)1, IRS2, phosphatidylinositol 3-kinase and AKT in liver and skeletal muscle], oral glucose stimulated insulin secretion, beta-cell morphology (mass, apoptosis and insulin secretion), glucagon-like peptide (GLP)-1, PYY and ghrelin were compared among SG rats with common low-fat diet (SG-LFD), SG with HFD (SG-HFD), DJB rats with LFD (DJB-LFD), DJB with HFD (DJB-HFD) and sham-operation with LFD (Sham) at targeted postoperative times.. SG and DJB resulted in significant improvement in glucose tolerance, lower HOMA-IR, up-regulated hepatic and muscular insulin signaling, higher levels of oral glucose-stimulated insulin secretion, bigger beta-cell mass, higher immunofluorescence intensity of insulin, fewer transferase-mediated dUTP-biotin 3' nick end-labeling (TUNEL)-positive beta cells and higher postprandial GLP-1 and PYY levels than in the Sham group. The improvement in glucose tolerance was reversed at 12 wk postoperatively. Compared with the SG-LFD and DJB-LFD groups, the SG-HFD and DJB-HFD groups showed higher HOMA-IR, down-regulated hepatic and muscular insulin signaling, and more TUNEL-positive beta cells. No significant difference was detected between HFD and LFD groups for body weight, glucose-stimulated insulin secretion, beta-cell mass, immunofluorescence intensity of insulin, and postprandial GLP-1 and PYY levels. Fasting serum ghrelin decreased in SG groups, and there was no difference between HFD-SG and LFD-SG groups.. HFD reverses the improvement in glucose homeostasis after SG and DJB. Diabetes recurrence may correlate with re-impaired insulin sensitivity, but not with alterations of beta-cell function and body weight.

Topics: Animals; Apoptosis; Bariatric Surgery; Body Weight; Diabetes Mellitus, Experimental; Diet, High-Fat; Duodenum; Gastrectomy; Ghrelin; Glucagon-Like Peptide 1; Glucose; Glucose Tolerance Test; Homeostasis; Insulin; Insulin Resistance; Insulin-Secreting Cells; Jejunum; Liver; Muscles; Peptide YY; Rats; Recurrence; Remission Induction; Signal Transduction; Streptozocin

Whey protein promotes weight loss and improves diabetic control, however, less is known of its bioactive components that produce such benefits. We compared the effects of normal protein (control) diet with high protein diets containing whey, or its fractions lactalbumin and lactoferrin, on energy balance and metabolism. Diet-induced obese rats were randomized to isocaloric diets: Control, Whey, Lactalbumin, Lactoferrin, or pair-fed to lactoferrin. Whey and lactalbumin produced transient hypophagia, whereas lactoferrin caused prolonged hypophagia; the hypophagia was likely due to decreased preference. Lactalbumin decreased weight and fat gain. Notably, lactoferrin produced sustained weight and fat loss, and attenuated the reduction in energy expenditure associated with calorie restriction. Lactalbumin and lactoferrin decreased plasma leptin and insulin, and lactalbumin increased peptide YY. Whey, lactalbumin and lactoferrin improved glucose clearance partly through differential upregulation of glucoregulatory transcripts in the liver and skeletal muscle. Interestingly, lactalbumin and lactoferrin decreased hepatic lipidosis partly through downregulation of lipogenic and/or upregulation of β-oxidation transcripts, and differentially modulated cecal bacterial populations. Our findings demonstrate that protein quantity and quality are important for improving energy balance. Dietary lactalbumin and lactoferrin improved energy balance and metabolism, and decreased adiposity, with the effects of lactoferrin being partly independent of caloric intake.

Topics: Adiposity; Animals; Body Weight; Diet; Energy Intake; Energy Metabolism; Insulin; Lactalbumin; Lactoferrin; Leptin; Male; Obesity; Peptide YY; Rats; Whey Proteins

Topics: Amino Acid Sequence; Animals; Anti-Obesity Agents; Body Weight; Diet; Inhibitory Concentration 50; Male; Mice; Mice, Knockout; Molecular Structure; Peptide YY

Dietary supplementation with fermentable carbohydrate protects against body weight gain. Fermentation by the resident gut microbiota produces short-chain fatty acids, which act at free fatty acid receptor 2 (FFAR2). Our aim was to test the hypothesis that FFAR2 is important in regulating the beneficial effects of fermentable carbohydrate on body weight and to understand the role of gut hormones PYY and GLP-1.. Wild-type or. We provide new mechanistic insight into how fermentable carbohydrate regulates metabolism. Using mice that lack FFAR2, we demonstrate that the fermentable carbohydrate inulin acts via this receptor to drive an 87% increase in the density of cells that produce the appetite-suppressing hormone peptide YY (PYY), reduce food intake, and prevent diet-induced obesity.. Our results demonstrate that FFAR2 is predominantly involved in regulating the effects of fermentable carbohydrate on metabolism and does so, in part, by enhancing PYY cell density and release. This highlights the potential for targeting enteroendocrine cell differentiation to treat obesity.

Topics: Animals; Body Weight; Colon; Dietary Carbohydrates; Dietary Supplements; Eating; Fatty Acids, Volatile; Fermentation; Fermented Foods; Gastrointestinal Hormones; Gastrointestinal Microbiome; Glucagon-Like Peptide 1; Inulin; Male; Mice; Mice, Knockout; Obesity; Peptide YY; Receptors, Cell Surface; Weight Gain

(1) The objective of this study is to analyze differences in smell-taste capacity between females in extreme weight/eating conditions (EWC) and (2) to explore the interaction between smell/taste capacity, gastric hormones, eating behavior and body mass index (BMI). The sample comprised 239 females in EWC [64 Anorexia nervosa (AN) and 80 age-matched healthy-weight controls, and 59 obese and 36 age-matched healthy-weight controls]. Smell and taste assessments were performed through "Sniffin' Sticks" and "Taste Strips," respectively. The assessment measures included the eating disorders inventory-2, the symptom check list 90-revised, and The Dutch Eating Behavior Questionnaire, as well as peptides from the gastrointestinal tract [Ghrelin, peptide YY, cholecystokinin]. Smell capacity was differentially associated across EWC groups. Smell was clearly impaired in obese participants and increased in AN (hyposmia in Obesity was 54.3 and 6.4 % in AN), but taste capacity did not vary across EWC. Ghrelin levels were significantly decreased in obese subjects and were related to smell impairment. EWC individuals showed a distinct smell profile and circulating ghrelin levels compared to controls. Smell capacity and ghrelin may act as moderators of emotional eating and BMI.

Topics: Adolescent; Adult; Anorexia Nervosa; Body Weight; Cholecystokinin; Feeding Behavior; Female; Ghrelin; Humans; Middle Aged; Obesity; Olfaction Disorders; Peptide YY; Smell; Taste; Taste Disorders; Young Adult

Chronic exposure to lipopolysaccharide (LPS) contributes to metabolic abnormalities, but there has been no study to evaluate plasma LPS levels after ileal transposition (IT). We examined the effect of IT on gut hormone secretion and plasma LPS levels and their correlation with metabolic parameters.. Sprague-Dawley rats underwent either IT or sham operation. After 4 weeks, oral glucose tolerance tests (OGTT) were performed and fasting plasma LPS and gut histology were analyzed.. Compared with the sham group, food intake and body weight decreased, and insulin sensitivity increased in the IT group. During the OGTTs, glucagon, glucagon-like peptide-1 (GLP-1), GLP-2, and peptide YY (PYY) were significantly higher in the IT group than the sham group. The villi length, muscle thickness, and the density of GLP-1 and glucose-dependent insulinotropic polypeptide co-expressing cells (K/L-cells) increased in the transposed ileum compared with the ileum of the sham group. Fasting plasma LPS levels were lower in the IT group than the sham group (5.6 ± 0.2 vs. 6.8 ± 0.1 EU/ml, P = 0.002) and significantly correlated with insulin resistance (r = 0.755, P < 0.001). Plasma LPS levels were negatively correlated with PYY secretion (r = -0.710, P = 0.001), and GLP-2 secretion (r = -0.561, P = 0.019).. IT surgery decreased plasma LPS levels in a non-obese non-diabetic rat model, which was associated with improved insulin sensitivity and increased L-cell secretion.

Topics: Animals; Blood Glucose; Body Weight; Drinking; Eating; Enteroendocrine Cells; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Glucose Tolerance Test; Ileum; Insulin Resistance; Lipopolysaccharides; Male; Obesity, Morbid; Peptide YY; Rats, Sprague-Dawley

The Thrifty Phenotype Hypothesis proposes that the fetus takes cues from the maternal environment to predict its postnatal environment. A mismatch between the predicted and actual environments precipitates an increased risk of chronic disease. Our objective was to determine if, following a high fat, high sucrose (HFS) diet challenge in adulthood, re-matching offspring to their maternal gestational diet would improve metabolic health more so than if there was no previous exposure to that diet. Animals re-matched to a high prebiotic fiber diet (HF) had lower body weight and adiposity than animals re-matched to a high protein (HP) or control (C) diet and also had increased levels of the satiety hormones GLP-1 and PYY (p < 0.05). Control animals, whether maintained throughout the study on AIN-93M, or continued on HFS rather than reverting back to AIN-93M, did not differ from each other in body weight or adiposity. Overall, the HF diet was associated with the most beneficial metabolic phenotype (body fat, glucose control, satiety hormones). The HP diet, as per our previous work, had detrimental effects on body weight and adiposity. Findings in control rats suggest that the obesogenic potential of the powdered AIN-93 diet warrants investigation.

Topics: Adiposity; Animal Nutritional Physiological Phenomena; Animals; Body Weight; Diet; Dietary Fats; Dietary Fiber; Dietary Proteins; Dietary Sucrose; Feeding Behavior; Female; Glucagon-Like Peptide 1; Lactation; Male; Maternal Nutritional Physiological Phenomena; Peptide YY; Prebiotics; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Satiety Response

Alternate day fasting (ADF; 25% energy intake "fast day", alternated with an ad libitum intake "feed day") is effective for weight loss. Whether or not ADF modulates hunger, fullness and gut peptides in a way that enhances dietary compliance and weight loss, remains unknown. Accordingly, this study examined the effect of ADF on postprandial appetite ratings and gut peptides.. Obese subjects (n = 59) participated in an 8-week ADF protocol where food was provided on the fast day.. Body weight decreased (P < 0.0001) by 3.9 ± 0.6 kg after 8 weeks of diet. Reductions (P < 0.05) in fat mass (-2.2 ± 0.2 kg), fat free mass (-1.4 ± 0.2 kg), visceral fat mass (-0.1 ± 0.1 kg), and resting metabolic rate (RMR; -104 ± 28 kcal/day) were also observed. Fasting leptin and insulin decreased (P < 0.05), while AUC ghrelin levels increased (P < 0.05). Despite these metabolic changes, there was no increase in subjective hunger by the end of the study. Furthermore, fullness and PYY increased (P < 0.05). Fat free mass and RMR were not related to hunger or ghrelin at any time point.. These findings suggest that the absence of a compensatory increase in hunger in conjunction with an increase in sensations of fullness may contribute to the weight loss efficacy of an 8-week ADF regimen.

Topics: Basal Metabolism; Blood Glucose; Body Composition; Body Mass Index; Body Weight; Diet; Diet Records; Exercise; Fasting; Female; Ghrelin; Humans; Hunger; Insulin; Leptin; Male; Middle Aged; Patient Compliance; Peptide YY; Satiation

Nutrition-related studies avoid the participation of pre-menopausal women due to the potential effect of the menstrual cycle (MC) on their appetite regulation. It is generally accepted that women increase their energy intake during the luteal phase (LPh) compared to the follicular (FPh), however what happens in the menstrual phase (MPh) and how this might be regulated remains uncertain. Although some research indicates changes in the gastric emptying (GE) velocity, whether PYY is affected by the MC phase, remains unknown. The aim of this study was to assess whether eating the same breakfast in each of the three MC phases would change the GE time, the PYY response and post-prandial satiety such that they might affect subsequent food intake. Furthermore, the aim was to associate any potential differences to the fluctuations in estradiol (E

Topics: Adolescent; Adult; Appetite; Appetite Regulation; Body Composition; Body Mass Index; Body Weight; Breakfast; Diet Records; Estradiol; Exercise; Female; Gastric Emptying; Humans; Menstrual Cycle; Peptide YY; Postprandial Period; Progesterone; Satiation; Surveys and Questionnaires; Young Adult

Intestinal nutrient infusions result in variable decreases in energy intake and body weight based on nutrient type and specific intestinal infusion site.. The objective was to test whether an intrajejunal fructose infusion (FRU) would lower energy intake and body weight and induce similar increases in gut hormones as those found after intrajejunal glucose infusions (GLU).. Male Sprague-Dawley rats received an intrajejunal infusion of either an equal kilocalorie load of glucose or fructose (11.4 kcal) or saline (SAL) for 5 d while intake of a standard rodent diet was continuously recorded; body weight was measured daily. Immediately after the infusion on the final day, rats were killed and plasma was collected to measure hormones.. Daily energy intake was significantly lower in the GLU group than in the SAL group, but the FRU group did not differ from the GLU or SAL groups when the 11.4 kcal of the infusate was included as energy intake. Lower energy intake was due to smaller meal sizes during the infusion period in the GLU group than in the FRU and SAL groups; the FRU and SAL groups did not differ. The percentage of change in body weight was lower in the GLU group than in the FRU and SAL groups. Plasma glucagon-like-peptide 1 (GLP-1) concentrations were greater in the GLU group than in the SAL group; the FRU group did not differ from the GLU or SAL groups. The plasma insulin concentration was greater in the FRU group than in both the GLU and SAL groups.. These results demonstrate that glucose induces a greater decrease in energy intake and increase in GLP-1 at distal intestinal sites than fructose in rats, which may explain differential effects of these monosaccharides between studies when delivered orally or along the proximal to distal axis of the intestine.

Topics: Animals; Blood Glucose; Body Weight; Energy Intake; Fructose; Glucagon-Like Peptide 1; Glucose; Insulin; Islet Amyloid Polypeptide; Jejunum; Male; Peptide YY; Rats; Rats, Sprague-Dawley

Intake of sodas has been shown to increase energy intake and to contribute to obesity in humans and in animal models, although the magnitude and importance of these effects are still debated. Moreover, intake of sugar sweetened beverages is often associated with high-fat food consumption in humans. We studied two different accesses to a sucrose-sweetened water (SSW, 12.3%, a concentration similar to that usually found in sugar sweetened beverages) in C57BL/6 mice fed a normal-fat (NF) or a high-fat (HF) diet in a scheduled access (7.5h). NF-fed and HF-fed mice received during 5weeks access to water, to SSW continuously for 7.5h (SSW), or to water plus SSW for 2h (randomly-chosen time slot for only 5 random days/week) (SSW-2h). Mouse preference for SSW was greater in HF-fed mice than NF-fed mice. Continuous SSW access induced weight gain whatever the diet and led to greater caloric intake than mice drinking water in NF-fed mice and in the first three weeks in HF-fed mice. In HF-fed mice, 2h-intermittent access to SSW induced a greater body weight gain than mice drinking water, and led to hyperphagia on the HF diet when SSW was accessible compared to days without SSW 2h-access (leading to greater overall caloric intake), possibly through inactivation of the anorexigenic neuropeptide POMC in the hypothalamus. This was not observed in NF-fed mice, but 2h-intermittent access to SSW stimulated the expression of dopamine, opioid and endocannabinoid receptors in the nucleus accumbens compared to water-access. In conclusion, in mice, a sucrose solution provided 2h-intermittently and a high-fat diet have combined effects on peripheral and central homeostatic systems involved in food intake regulation, a finding which has significant implications for human obesity.

Topics: Animals; Body Composition; Body Weight; Brain; Cholecystokinin; Diet, High-Fat; Drinking Behavior; Eating; Energy Intake; Feeding Behavior; Food Deprivation; Gene Expression Regulation; Ghrelin; Leptin; Male; Mice; Mice, Inbred C57BL; Peptide YY; Sucrose; Sweetening Agents; Time Factors

The aim of this study was to investigate effects and mechanisms of chronic electrical stimulation at acupoints (CEA) using surgically implanted electrodes on food intake, body weight, and metabolisms in diet-induced obese (DIO) rats.. Thirty-six DIO rats were chronically implanted with electrodes at acupoints ST-36 (Zusanli). Three sets of parameters were tested: electrical acupuncture (EA) 1 (2-s on, 3-s off, 0.5 ms, 15 Hz, 6 mA), EA2 (same as EA1 but continuous pulses), and EA3 (same as EA2 but 10 mA). A chronic study was then performed to investigate the effects of CEA on body weight and mechanisms involving gastrointestinal hormones and autonomic functions.. EA2 significantly reduced food intake without uncomfortable behaviors. CEA at EA2 reduced body weight and epididymal fat pad weight (P < 0.05). CEA reduced both postprandial blood glucose and HbA1c (P < 0.05). CEA delayed gastric emptying (P < 0.03) and increased small intestinal transit (P < 0.02). CEA increased fasting plasma level of glucagon-like peptide-1 (GLP-1) and peptide YY (P < 0.05); the increase of GLP-1 was inversely correlated with postprandial blood glucose (R (2) = 0.89, P < 0.05); and the plasma ghrelin level remained unchanged. EA increased sympathetic activity (P < 0.01) and reduced vagal activity (P < 0.01).. CEA at ST-36 reduces body weight and improves blood glucose possibly attributed to multiple mechanisms involving gastrointestinal motility and hormones via the autonomic pathway.

Topics: Acupuncture Points; Animals; Autonomic Nervous System; Blood Glucose; Body Weight; Eating; Electric Stimulation Therapy; Fasting; Gastrointestinal Motility; Ghrelin; Glucagon-Like Peptide 1; Male; Obesity; Obesity, Morbid; Peptide YY; Postprandial Period; Rats; Rats, Sprague-Dawley; Vagus Nerve

In addition to classic functions of facilitating hepatobiliary secretion and intestinal absorption of lipophilic nutrients, bile acids (BA) are also endocrine factors and regulate glucose and lipid metabolism. Recent data indicate that antiobesity bariatric procedures e.g. Roux-en-Y gastric bypass surgery (RYGB), which also remit diabetes, increase plasma BAs in humans, leading to the hypothesis that BAs may play a role in diabetes resolution following surgery. To investigate the effect of RYGB on BA physiology and its relationship with glucose homeostasis, we undertook RYGB and SHAM surgery in Zucker diabetic fatty (ZDF) and normoglycemic Sprague Dawley (SD) rats and measured plasma and fecal BA levels, as well as plasma glucose, insulin, Glucagon like peptide 1 (GLP-1) and Peptide YY (PYY), 2 days before and 3, 7, 14 and 28 days after surgery. RYGB decreased body weight and increased plasma GLP-1 in both SD and ZDF rats while decreasing plasma insulin and glucose in ZDF rats starting from the first week. Compared to SHAM groups, both SD-RYGB and ZDF-RYGB groups started to have increases in plasma total BAs in the second week, which might not contribute to early post-surgery metabolic changes. While there was no significant difference in fecal BA excretion between SD-RYGB and SD-SHAM groups, the ZDF-RYGB group had a transient 4.2-fold increase (P<0.001) in 24-hour fecal BA excretion on post-operative day 3 compared to ZDF-SHAM, which paralleled a significant increase in plasma PYY. Ratios of plasma and fecal cholic acid/chenodeoxycholic acid derived BAs were decreased in RYGB groups. In addition, tissue mRNA expression analysis suggested early intestinal BA reabsorption and potentially reduced hepatic cholic acid production in RYGB groups. In summary, we present novel data on RYGB-mediated changes in BA metabolism to further understand the role of BAs in RYGB-induced metabolic effects in humans.

Topics: Animals; Bile Acids and Salts; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Disease Models, Animal; Gastric Bypass; Gastric Inhibitory Polypeptide; Gene Expression Profiling; Glucagon-Like Peptide 1; Insulin; Organ Specificity; Peptide YY; Rats

Monoacylglycerol acyltransferase 2 (MGAT2) plays an important role in intestinal fat absorption. We discovered the novel MGAT2 inhibitor, JTP-103237, and evaluated its pharmacological profile. JTP-103237 selectively inhibited MGAT2 without remarkable species differences and reduced absorbed lipids in circulation. After lipid administration, JTP-103237 slightly but significantly decreased triglyceride content in proximal small intestine and significantly increased the lipids content in the distal small intestine. In addition, JTP-103237 significantly increased MGAT substrate (monoacylglycerol and fatty acid) content in the small intestine. JTP-103237 increased plasma peptide YY levels after lipid loading and reduced food intake in a dietary fat-dependent manner. After chronic treatment, JTP-103237 significantly decreased body weight and increased O2 consumption in the early dark phase in high fat diet induced obese (DIO) mice. Moreover, JTP-103237 improved glucose tolerance and decreased fat weight and hepatic triglyceride content in DIO mice. Our findings indicate that JTP-103237 prevents diet-induced obesity by inhibiting intestinal MGAT2 and has unique properties as a drug for the treatment of obesity.

Topics: Acyltransferases; Animals; Body Weight; Chlorocebus aethiops; COS Cells; Diet, High-Fat; Eating; Glucose Tolerance Test; Humans; Intestinal Absorption; Lipid Metabolism; Male; Mice; Obesity; Oxygen Consumption; Peptide YY; Piperazines; Rats; Triazoles

Hyperemesis gravidarum (HG) is described as unexplained excessive nausea and vomiting during pregnancy. Some gut hormones that regulate appetite may have important role in etiopathogenesis of HG and weight changes during pregnancy. In this study, levels of gut satiety hormones were evaluated in pregnant women with HG.. This prospective case-control study was conducted in 30 women with HG and 30 healthy pregnant women without symptoms of HG. Fasting venous blood samples were taken from all subjects for measurement of plasma gut hormone levels; obestatin (pg/mL), peptide YY (PYY), pancreatic polypeptide (PP) and cholecystokinin (CCK).. Plasma PYY and PP levels were significantly higher in HG group. The most important parameter in diagnosis of HG was plasma PP level. Simple use of PP level led to the diagnosis 91.1 % of HG cases correctly. The single most important parameter in the prediction of HG was also PP level.. Anorexigenic gut hormones might have important role in etiopathogenesis of hyperemesis gravidarum and weight changes during pregnancy.

Topics: Adult; Body Weight; Case-Control Studies; Cholecystokinin; Fasting; Female; Ghrelin; Humans; Hyperemesis Gravidarum; Pancreatic Polypeptide; Peptide YY; Pregnancy; Prospective Studies; Weight Gain; Young Adult

Dietary fat supplementation during the periparturient period is one strategy to increase energy intake and attenuate the degree of negative energy balance during early lactation; however, little is known of the underlying hormonal and metabolic adaptations. We evaluated the effects of prepartum fat supplementation on energy-balance parameters and plasma concentrations of glucagon-like peptide-1, peptide tyrosine-tyrosine (PYY), adropin, insulin, leptin, glucose, nonesterified fatty acid, and β-hydroxybutyric acid in dairy cows. Twenty-four pregnant dairy cows were randomized to diets containing either rolled canola or sunflower seed at 8% of dry matter, or no oilseed supplementation, during the last 5 wk of gestation and then assigned to a common lactation diet postpartum. Blood samples were collected at -2, +2, and +14 h relative to feeding, at 2 wk after the initiation of the diets, and at 2 wk postpartum. Dietary canola and sunflower supplementation alone did not affect energy balance, body weight, and plasma concentrations of glucagon-like peptide-1, PYY, adropin, insulin, leptin, nonesterified fatty acid, and β-hydroxybutyric acid; however, canola decreased and sunflower tended to decrease dry matter intake. We also observed that the physiological stage had a significant, but divergent, effect on circulating hormones and metabolite concentrations. Plasma glucagon-like peptide-1, PYY, adropin, nonesterified fatty acid, and β-hydroxybutyric acid concentrations were greater postpartum than prepartum, whereas glucose, insulin, leptin, body weight, and energy balance were greater prepartum than postpartum. Furthermore, the interaction of treatment and stage was significant for leptin and adropin, and tended toward significance for PYY and insulin; only insulin exhibited an apparent postprandial increase. Postpartum PYY concentrations exhibited a strong negative correlation with body weight, suggesting that PYY may be associated with body weight regulation during the transition period. These novel findings demonstrate that the transition from pregnancy to lactation is a stronger determinant of circulating gut hormone concentrations than dietary lipid in transition dairy cows.

Topics: 3-Hydroxybutyric Acid; Animals; Blood Proteins; Body Weight; Cattle; Diet; Dietary Fats; Dietary Supplements; Dipeptides; Energy Intake; Energy Metabolism; Fatty Acids, Nonesterified; Female; Glucagon-Like Peptide 1; Hormones; Insulin; Lactation; Leptin; Peptide YY; Postpartum Period; Pregnancy; Random Allocation

Breast-feeding is associated with maternal hormonal and metabolic changes ensuring adequate milk production. In this study, we investigate the impact of breast-feeding on the profile of changes in maternal appetite-regulating hormones 3-6 months postpartum. Study participants were age- and BMI-matched lactating mothers (n 10), non-lactating mothers (n 9) and women without any history of pregnancy or breast-feeding in the previous 12 months (control group, n 10). During study sessions, young mothers breast-fed or bottle-fed their babies, and maternal blood samples were collected at five time points during 90 min: before, during and after feeding the babies. Outcome parameters were plasma concentrations of ghrelin, peptide YY (PYY), leptin, adiponectin, prolactin, cortisol, insulin, glucose and lipid values. At baseline, circulating PYY concentrations were significantly increased in lactating mothers (100·3 (se 6·7) pg/ml) v. non-lactating mothers (73·6 (se 4·9) pg/ml, P=0·008) and v. the control group (70·2 (se 9) pg/ml, P=0·021). We found no differences in ghrelin, leptin and adiponectin values. Baseline prolactin concentrations were over 4-fold higher in lactating mothers (P<0·001). Lactating women had reduced TAG levels and LDL-cholesterol:HDL-cholesterol ratio, but increased waist circumference, when compared with non-lactating women. Breast-feeding sessions further elevated circulating prolactin (P<0·001), but induced no acute effects on appetite-regulating hormones. In summary, one single breast-feeding session did not acutely modulate circulating appetite-regulating hormones, but increased baseline PYY concentrations are associated with prolonged lactation. PYY might play a role in the coordination of energy balance during lactation, increasing fat mobilisation from maternal depots and ensuring adequate milk production for the demands of the growing infant.

Topics: Adiponectin; Adult; Appetite; Blood Glucose; Body Mass Index; Body Weight; Breast Feeding; Cholesterol, HDL; Cholesterol, LDL; Cohort Studies; Female; Ghrelin; Humans; Hydrocortisone; Infant; Insulin; Lactation; Leptin; Peptide YY; Postpartum Period; Pregnancy; Prolactin; Triglycerides; Waist Circumference

Deoxynivalenol (DON), a trichothecene mycotoxin that commonly contaminates cereal grains, is a public health concern because of its adverse effects on the gastrointestinal and immune systems. The objective of this study was to compare effects of DON on anorectic responses in aged (22 mos) and adult (3 mos) mice. Aged mice showed increased feed refusal with both acute i.p. (1 mg/kg and 5 mg/kg) and dietary (1, 2.5, 10 ppm) DON exposure in comparison to adult mice. In addition to greater suppression of food intake from dietary DON exposure, aged mice also exhibited greater but transient body weight suppression. When aged mice were acutely exposed to 1 mg/kg bw DON i.p., aged mice displayed elevated DON and DON3GlcA tissue levels and delayed clearance in comparison with adult mice. Acute DON exposure also elicited higher proinflammatory cytokine and satiety hormone responses in the plasma of the aged group compared with the adult group. Increased susceptibility to DON-induced anorexia in aged mice relative to adult mice suggests that advanced life stage could be a critical component in accurate human risk assessments for DON and other trichothecenes.

Topics: Aging; Animals; Anorexia; Body Weight; Cholecystokinin; Cytokines; Eating; Male; Mice, Inbred C57BL; Peptide YY; Satiety Response; Tissue Distribution; Trichothecenes

To elucidate the specific role of gastric vs. intestinal manipulations in the regulation of body weight and glucose homeostasis.. The effects of intestinal bypass alone (duodenal-jejunal bypass -DJB) and gastric resection alone (SG) in Zucker Diabetic Fatty (ZDF) rats were compared. Additional animals underwent a combination procedure (SG + DJB). Outcome measures included changes in weight, food intake (FI), oral glucose tolerance (GT) and gut hormones.. DJB did not substantially affect weight and FI, whereas SG significantly reduced weight gain and food consumption. DJB rats showed weight-independent improvement in GT, which improved less after SG. Furthermore, SG significantly suppressed plasma ghrelin and increased insulin, glucagon like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide and peptide YY response to oral glucose whereas DJB had no effects on postprandial levels of these hormones. DJB restored postprandial glucagon suppression in diabetic rats whereas SG did not affect glucagon response. The combination procedure (SG + DJB) induced greater weight loss and better GT than SG alone without reducing food intake further.. These findings reveal a dominant role of the stomach in the regulation of body weight and incretin response to oral glucose whereas intestinal bypass primarily affects glucose homeostasis by a weight-, insulin- and incretin-independent mechanism.

Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Duodenum; Gastrectomy; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon-Like Peptide 1; Glucose Tolerance Test; Homeostasis; Insulin; Jejunoileal Bypass; Jejunum; Male; Obesity; Peptide YY; Postoperative Care; Rats

Crude extracts from ginseng demonstrated anti-obesity properties. Ginsenoside Rb1 is the main component of ginseng, however, there are only few studies examining its effects in obesity. In the present study, we evaluated its potential anti-obesity effects in the murine model of diet-induced obesity. Seventy male C57BL/6 mice were randomly divided to consume for 12 weeks either chow diet (N = 8) or high-fat (HF) diet (N = 62). The latter mice were then divided into four groups: diet-induced obesity group (DIO; N = 10), obesity-resistant group (OR; N = 10), HF group (N = 5), and the group whose diet was changed from HF to normal diet (DC; N = 5). Intraperitoneal injections of Rb-1 were administered daily to mice in the DIO and OR groups for 3 weeks. Body weight and energy intake were monitored, and fasting blood glucose, lipids, neuropeptide Y, Y2 receptor, and peptide YY were quantified. Compared with HF group, weight gain and food intake of DIO mice with Rb-1 injection was significantly decreased (p < 0.05). Further, levels of blood glucose and some lipids were also decreased in DIO-Rb1 group compared with HF group. Furthermore, Rb1 was also found to modulate serum levels of PYY and NPY, and mRNA expression of NPY, Y2 receptor and PYY in tissue samples of DIO mice. Taken together, ginsenoside Rb1 may be useful in the treatment of obesity via modifying the serum content and mRNA expression of NPY, Y2 receptor and PYY.

Topics: Animals; Blood Glucose; Body Weight; Diet; Diet, High-Fat; Drug Administration Schedule; Ginsenosides; Injections, Intraperitoneal; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Neuropeptide Y; Obesity; Panax; Peptide YY; Receptors, Neuropeptide Y

To stop smoking is commonly associated with significant weight gain, but the mechanisms for this are poorly understood. We assessed the effects of smoking cessation on body weight, insulin sensitivity, β-cell function, and appetite.. Twenty-seven long-term smokers (n=27; nine females/18 males, 28±1 years, 22.9±0.6 kg/m(2)) attending an ambulatory smoking cessation program in a community hospital in Vienna, Austria were examined at baseline (Visit A; still smoking) and after a minimum of 3 months of smoking abstinence (Visit B; n=14); relapsed smokers were not followed up. Participants underwent 3-h oral glucose tolerance tests and body composition measurements at each study visit. Fasting (QUICKI) and dynamic (oral glucose insulin sensitivity (OGIS)) insulin sensitivity and β-cell secretion (insulinogenic index 140 (IGI40)) were calculated. Food intake was quantified with a free choice buffet. Fasting plasma concentrations of neuropeptide-Y (NPY), peptide-YY (PYY), glucagon-like peptide 1 (GLP1), leptin, ghrelin, and visfatin were measured.. AFTER 3 MONTHS' SMOKING ABSTINENCE, BODY WEIGHT, AND FAT MASS WERE INCREASED (+4 AND +22% RESPECTIVELY, P0.05) AND FASTING INSULIN SENSITIVITY DETERIORATED (QUICKI: post, 0.37±0.02 vs baseline, 0.41±0.2; P<0.05), while OGIS remained unchanged throughout. IGI40 increased by 31% after >3 months' smoking abstinence (P<0.01). Carbohydrate ingestion increased after stopping smoking (P<0.05). NPY fasting levels were increased after >3 months (P<0.05), PYY, GLP1, leptin, ghrelin, and visfatin were unchanged.. Smoking cessation is associated with transient metabolic changes including increased β-cell secretion in response to glucose and fasting insulin resistance. These alterations may be associated with or contribute to the body weight gain after smoking cessation.

Topics: Adult; Appetite; Body Weight; Eating; Female; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Leptin; Male; Neuropeptide Y; Peptide YY; Smoking Cessation

Intestinal nutrient infusions result in variable decreases in food intake and body weight based on the nutrient type and the specific intestinal infusion site. We previously found that intrajejunal infusions of a fatty acid and glucose, but not casein hydrolysate, decreases food intake and body weight in lean chow-fed laboratory rats. To test whether obese, high fat-fed animals would show similar decreases in food intake and body weight in response to intrajejunal infusions of the same nutrients, equal kilocalorie loads of these nutrients (11.4 kcal) or vehicle were infused into the jejunum of obese, high fat-fed male Sprague-Dawley rats over 7 h/day for 5 consecutive days. Food intake was continuously monitored, and body weight was measured daily. After the infusion on the final day, rats were killed and plasma was collected. Similar to lean chow-fed rats, intrajejunal infusions of linoleic acid (LA) and glucose (Glu), but not casein hydrolysate (Cas), suppressed food intake with no compensatory increase in food intake after the infusion period. In contrast to lean chow-fed rats, only the LA, and not the Glu or Cas, produced decreases in body weight in the obese high fat-fed rat. There also were no differences in plasma glucagon-like peptide-1 levels in any of the nutrient infusion groups compared with saline infusion. These results suggest that there is a differential response to the same nutrients in lean vs. obese animals.

Topics: Animals; Body Weight; Caseins; Eating; Endocrine System; Enteral Nutrition; Glucagon-Like Peptide 1; Glucose; Jejunum; Linoleic Acid; Male; Obesity; Peptide YY; Rats; Rats, Sprague-Dawley; Satiation

The aim of this study was to develop a novel surgical model to test the "hindgut hypothesis" and thereby study the role of the gut in glucose homeostasis and the mechanism of action of bariatric surgery.. Sprague-Dawley rats were given a high-fat and high-sugar diet and treated with 25 mg/kg streptozotocin (STZ). The fat-sugar-fed/STZ-treated rats were randomized into mid to distal small bowel resection with the preservation of the terminal ileum (DBRPI) and sham operation (which had a formal celiotomy with bowel manipulation only) groups. Rats were observed for 12 weeks after the operation. The main outcome measures were weight, food intake, non-fasting glucose, an oral glucose tolerance test (OGTT), an insulin tolerance test (ITT), the levels of fasting and glucose-induced insulin, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), serum bile acids, and lipid profile.. The DBRPI and sham groups exhibited no difference in weight and food intake after surgery. When compared to the sham controls, the DBRPI group displayed an improvement in non-fasting glucose, oral glucose tolerance, and insulin tolerance at 4 and 12 weeks postresection. DBRPI elicited an increased serum insulin, PYY and GLP-1 levels at 12 weeks postoperation; furthermore, DBRPI resulted in higher serum levels of triglyceride, total bile acids, total bilirubin, and direct bilirubin levels and lower free fatty acid level at 12 weeks.. This study provides strong evidences for the key role of hindgut in the amelioration of diabetes after bariatric surgery. Moreover, these findings confirm that DBRPI is a simple and effective surgical model for testing the "hindgut hypothesis" and focused study of biliary enterohepatic recycling in the context of bariatric operations.

Topics: Animals; Bile Acids and Salts; Bilirubin; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Eating; Fatty Acids, Nonesterified; Glucagon-Like Peptide 1; Glucose Tolerance Test; Homeostasis; Ileum; Insulin; Jejunum; Liver Function Tests; Models, Animal; Organ Sparing Treatments; Peptide YY; Rats; Rats, Sprague-Dawley; Triglycerides

The objective of this study was to evaluate the association between insulin-resistance and fasting levels of ghrelin and PYY in Wistar rats.. A total of 25 male Wistar rats, weighing 200-300 g, was included in this study. The animals were maintained in cages with a 12/12h light-dark cycle and fed standard chow and water ad libitum. After 12-h overnight fasting, ghrelin, PYY, insulin and glucose values were determined. Insulin resistance was assessed by means of the HOMA-IR, which was ranked and the median was used as a cut-off value to categorize insulin-resistance. HOMA-IR values equal and above 2.62 were considered insulin-resistant (IR) while values below 2.62 were considered insulin sensitive (IS). Differences between means were determined using the Student t-test. Multiple regression and Pearson's correlation test were used to evaluate the association between variables.. HOMA-IR median IQ range values for IS and IR groups were, respectively, 1.56 (0.89 - 2.16) vs. [4.06 (3.50 - 4.61); p < 0.001]. The IR group presented increased levels of fasting ghrelin, PYY and insulin respectively: [50.35 (25.99 - 74.71) pg/mL vs. 12.33 (8.77 - 15.89) pg/mL; p = 0.001]; [54.38 (37.50 - 71.26) pg/mL vs. 33.17 (22.34 - 43.99) pg/mL; p = 0.016]; [18.04 (14.48 - 21.60) uU/mL vs. 7.09 (4.83 - 9.35) uU/mL; p = 0.001]. Ghrelin, but not PYY, correlated linearly and positively with HOMA-IR: ghrelin vs. HOMA-IR (r = 0.52; p = 0.008), and PYY vs. HOMA-IR (r = 0.22; p = 0.200). This correlation was independent of body weight.. Fasting ghrelin and PYY serum levels are increased in lean, relatively insulin resistant Wistar rats, and this increase is independent of weight.

Topics: Animals; Blood Glucose; Body Weight; Cross-Sectional Studies; Fasting; Ghrelin; Insulin; Insulin Resistance; Male; Peptide Fragments; Peptide YY; Rats, Wistar; Regression Analysis

The present study was undertaken to determine if patients with schizophrenia on clozapine monotherapy have lower serum levels of peptide YY [PYY(1-36)], which is an endogenous inhibitor of food intake, comparing to healthy controls.. Data for 24 patients (mean age 38.8 years) with paranoid schizophrenia on clozapine monotherapy and 24 healthy subjects (gender- and age-matched; mean age 39.9 years) were analyzed.. Fasting serum levels of PYY(1-36) were lower in the clozapine group (178.4±138.4 vs. 277.4±218.1 pg/mL, p=0.034). In the whole study sample PYY(1-36) levels were lower in subjects with body mass index≥25 kg/m(2) (p=0.03) and in subjects with abdominal obesity defined using International Diabetes Foundation criteria (p=0.04). There were no significant differences for metabolic syndrome, smoking, impaired fasting glucose, dyslipidemia, and homeostatic model assessment (HOMA) defined insulin resistance.. RESULTS suggest that weight is asso-ciated with levels of PYY. Patients on clozapine had higher body mass index, but not fat mass index or body weight, therefore lower levels of PYY(1-36) in patients taking clozapine may result from clozapine-induced weight gain and central -obesity.

Topics: Adult; Antipsychotic Agents; Body Composition; Body Mass Index; Body Weight; Clozapine; Electric Impedance; Female; Humans; Male; Metabolic Syndrome; Middle Aged; Peptide YY; Schizophrenia; Smoking

Using an adjustable stimulator with a wide range of stimulation parameters, the aims of this study were 1) to investigate the effects of long-term gastric electrical stimulation (GES) on appetite and differential food cravings for three different foods and 2) to investigate the effects of GES on plasma gastrointestinal peptide concentrations.. The study was performed in eight Beagle dogs implanted with one pair of serosal electrodes. They were followed during GES and sham GES sessions in a crossover design. GES was conducted using a series of individualized parameters. Food intake and food cravings were observed to evaluate the effects of long-term GES. Enzyme-linked immunosorbent assay was used to measure the plasma concentrations of gastrointestinal peptides.. Dogs on GES for three months ate significantly less food than those on sham GES for three months (p < 0.05). A significant change in food cravings was induced by GES. Dogs with GES ate significantly less high-fat food. However, there was no significant difference in consumption of high-carbohydrate food or balanced food between the periods of GES and sham GES. The plasma concentrations of ghrelin, peptide YY3-36, and glucagon-like peptide 1 did not differ significantly between the periods of GES and sham GES.. Food intake and food craving were changed significantly by adjustable GES. GES may be used for treating obesity by changing food preferences. Further clinical studies are necessary to highlight the effect of adjustable GES on eating behavior.

Topics: Animals; Biophysics; Body Weight; Craving; Dogs; Eating; Electric Stimulation; Electrodes, Implanted; Enzyme-Linked Immunosorbent Assay; Female; Ghrelin; Peptide Fragments; Peptide YY; Stomach

Cancer-associated anorexia and cachexia are a multifactorial condition described by a loss of body weight and muscle with anorexia, asthenia, and anemia. Moreover, they correlate with a high mortality rate, poor response to chemotherapy, poor performance status, and poor quality of life. Cancer cachexia is regulated by proinflammatory cytokines such as interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor- α (TNF- α). In addition, glucagon like peptide-1 (GIP-1), peptide YY (PYY), ghrelin, and leptin plays a crucial role in food intake. In this study, we investigated the therapeutic effects of one of the traditional herbal medicines, Sipjeondaebo-tang (Juzen-taiho-to in Japanese; SJDBT), on cancer anorexia and cachexia in a fundamental mouse cancer anorexia/cachexia model, CT-26 tumor-bearing mice. SJDBT was more significantly effective in a treatment model where it was treated after anorexia and cachexia than in a prevention model where it was treated before anorexia and cachexia on the basis of parameters such as weights of muscles and whole body and food intakes. Moreover, SJDBT inhibited a production of IL-6, MCP-1, PYY, and GLP-1 and ameliorated cancer-induced anemia. Therefore, our in vivo studies provide evidence on the role of SJDBT in cancer-associated anorexia and cachexia, thereby suggesting that SJDBT may be useful for treating cancer-associated anorexia and cachexia.

Topics: Animals; Anorexia; Body Weight; Cachexia; Cell Line, Tumor; Chemokine CCL2; Drugs, Chinese Herbal; Ghrelin; Glucagon-Like Peptide 1; Inflammation; Interleukin-6; Intestinal Mucosa; Leptin; Male; Mice; Mice, Inbred BALB C; Muscles; Neoplasm Transplantation; Neoplasms; Peptide YY; Plant Preparations; Tumor Necrosis Factor-alpha

Maternal protein restriction (PR) during pregnancy is known to have numerous adverse effects on offspring, including increased adiposity and impaired glucose tolerance later in life. A few studies have shown that this adverse programming can be reversed by dietary or hormonal therapies early in postnatal life. The objective of this study was to determine if a weaning diet high in prebiotic fiber could mitigate some of the negative effects of maternal PR, such as increased adiposity and impaired glucose tolerance. Wistar rats were fed a low- (8%) or normal- (20%) protein diet during pregnancy. Male and female pups were weaned onto control (C; 5% fiber, 20% protein) or high (prebiotic) fiber (HF; 21% wt:wt, 1:1 ratio oligofructose and inulin at 4-10 wk; 10% wt:wt, 1:1 ratio oligofructose and inulin at 10-24 wk; 17.3% protein) diets. At 24 wk of age, glucose tolerance, body composition, satiety hormones, gut microbiota, and markers of intestinal permeability were measured in the offspring. Maternal PR reduced offspring birth weight by 5% and lean mass by 9% compared with the C offspring (P < 0.007). HF-fed offspring had lower body weights and percentage body fat (∼23% in males, ∼19% in females) at 24 wk than did C offspring (P < 0.02). Compared with C pups, pups fed the HF diet had greater cecal Bifidobacterium spp. (>5-fold) and plasma concentrations of the gut trophic hormone glucagon-like peptide 2 (GLP-2) (P < 0.05). In male PR offspring fed the HF diet, insulin resistance measured by the homeostasis model assessment of insulin resistance was reduced by 81% compared with those fed the C diet (P = 0.02). In female PR offspring fed the HF diet, plasma endotoxin was greater and colonic tight junction protein 1 (Tjp1) expression was lower than in those fed the C diet. A high prebiotic fiber weaning diet mitigated increased adiposity and insulin resistance associated with maternal PR, which could improve health and decrease risk of chronic disease in offspring born to malnourished dams. However, the functional importance of sex-specific changes in markers of intestinal barrier function warrants further investigation.

Topics: Adiposity; Animals; Blood Glucose; Body Composition; Body Weight; Diet; Diet, High-Fat; Diet, Protein-Restricted; Dietary Fiber; Female; Gastrointestinal Tract; Ghrelin; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Insulin; Insulin Resistance; Male; Maternal Nutritional Physiological Phenomena; Peptide YY; Permeability; Prebiotics; Pregnancy; Rats; Rats, Wistar; Satiation; Sex Factors; Weaning

Dietary fiber may contribute to satiety. This study examined the effect of two dietary fiber characteristics, small intestinal contents viscosity and large intestinal fermentability, on satiety-and adiposity-related hormones in rats. Diets contained fiber sources that were non-viscous, somewhat viscous, or highly viscous, and either highly fermentable or non-fermentable, in a 2 × 3 factorial design. In the fed state (2 h postprandial), rats fed non-fermentable fibers had significantly greater plasma GLP-1 concentration than fermentable fibers. In the fasted state, among non-fermentable fibers, viscosity had no effect on GLP-1 concentration. However, among fermentable fibers, greater viscosity reduced GLP-1 concentration. Plasma peptide tyrosine tyrosine (PYY) concentrations in the fasted state were not influenced by the fermentability of the fiber overall, however animals consuming a fructooligosaccharide greater PYY concentration. In both the fed and fasted states, rats fed non-fermentable fibers had a significantly lower plasma ghrelin concentration than rats fed fermentable fibers. In the fasted state, rats fed non-fermentable fibers had a significantly lower plasma leptin concentration than rats fed fermentable fibers. Thus, fermentability and viscosity of dietary fiber interacted in complex ways to influence satiety- and adiposity-related plasma hormone concentrations. However, the results suggest that highly viscous, non-fermentable fibers may limit weight gain and reduce adiposity and non-fermentable fibers, regardless of viscosity, may promote meal termination.

Topics: Adiposity; Animals; Body Weight; Diet; Dietary Fiber; Fermentation; Ghrelin; Glucagon-Like Peptide 1; Insulin; Leptin; Male; Organ Size; Peptide YY; Rats; Rats, Wistar; Satiation; Viscosity

Peptide YY (PYY3-36) and pancreatic polypeptide (PP) potently inhibit food intake in rodents and humans, however, it is unclear whether they have any synergistic/additive interaction in decreasing food intake.. Fasted WT, Y2(-) (/) (-) , Y4(-) (/) (-) , or Y2Y4(-) (/) (-) mice were i.p. administrated with saline, PYY3-36, and/or PP.. Combined injection of PYY3-36 and PP reduces food intake in an additive manner was demonstrated in this study. This effect is mediated via Y2 and Y4 receptors, respectively. It was demonstrated that PYY3-36 and PP activate distinct neuronal pathways in the hypothalamus, as demonstrated by immunostaining for c-fos, which shows distinct patterns in response to either hormone. After PYY3-36 injection, neurons in the dorsal aspect of the arcuate nucleus (Arc), paraventricular nucleus, and dorso-medial nucleus of the hypothalamus (DMH) are activated with minimal responses seen in the ventro-medial nucleus of the hypothalamus (VMH) and lateral hypothalamic area (LHA) of WT mice. These effects are absent in Y2(-) (/) (-) mice. PP activates preferably the lateral aspect of the Arc, the DMH, VMH, and LHA in a Y4 receptor-dependent manner. Importantly, the expression pattern of c-fos immunoreactive neurons induced by combined treatment appears to be the sum of the effects of single treatments rather than a result of synergistic interaction.. These findings demonstrate that PYY3-36 and PP activate distinct pathways in the hypothalamus to reduce food intake in an additive manner.

Topics: Animals; Arcuate Nucleus of Hypothalamus; Body Weight; Eating; Fasting; Immunohistochemistry; Male; MAP Kinase Signaling System; Mice; Mice, Knockout; Neurons; Pancreatic Polypeptide; Paraventricular Hypothalamic Nucleus; Peptide Fragments; Peptide YY; Proto-Oncogene Proteins c-fos; Receptors, Neuropeptide Y

Ghrelin is an orexigenic peptide that stimulates food intake, whereas peptide YY (PYY) and cholecystokinin (CCK) are anorexigenic gut hormones. Patients with polycystic ovary syndrome (PCOS) appear to have alterations in appetite regulation.. We aimed to determine whether fasting or meal-stimulated ghrelin, PYY, CCK, and satiety responses are different between lean PCOS patients and healthy women. We also aimed to assess the potential effect of oral contraceptive use on these hormones and satiety response.. We conducted a prospective observational study in a university practice.. Eighteen lean PCOS patients and 18 healthy control women matched for age and body mass index underwent measurements of circulating ghrelin, PYY, CCK, and satiety index (SI) before and after a standardized mixed meal at 0, 15, 30, 45, 60, 90, 120, and 180 minutes.. For PCOS patients who were treated with ethinyl estradiol 30 μg/drospirenone 3 mg for 3 months, measurements were repeated.. We measured ghrelin, PYY, and CCK levels and SI.. At baseline, fasting ghrelin, PYY, CCK, and SI values in PCOS patients were not different from controls. Meal-stimulated PYY, CCK, and SI were also not different between the groups, whereas PCOS patients had significantly lower meal-stimulated ghrelin levels compared to controls (P = .04). Ghrelin, PYY, CCK, and SI did not show a significant change after treatment with ethinyl estradiol/drospirenone for 3 months.. Basal and stimulated hunger and satiety hormones in lean PCOS patients are not different from lean healthy women, except for a lower meal-stimulated ghrelin response. Short-term use of a low-dose oral contraceptive does not have an effect on appetite regulation of PCOS.

Topics: Adolescent; Adult; Androstenes; Basal Metabolism; Body Weight; Cholecystokinin; Contraceptives, Oral; Eating; Estrogens; Ethinyl Estradiol; Female; Ghrelin; Humans; Mineralocorticoid Receptor Antagonists; Peptide YY; Polycystic Ovary Syndrome; Prospective Studies; Satiety Response; Young Adult

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

Obesity and its associated conditions such as type 2 diabetes mellitus are major causes of morbidity and mortality. The iminosugar N-(5-adamantane-1-yl-methoxy-pentyl)-deoxynojirimycin (AMP-DNM) improves insulin sensitivity in rodent models of insulin resistance and type 2 diabetes mellitus. In the current study, we characterized the impact of AMP-DNM on substrate oxidation patterns, food intake, and body weight gain in obese mice. Eight ob/ob mice treated with 100 mg/(kg d) AMP-DNM mixed in the food and 8 control ob/ob mice were placed in metabolic cages during the first, third, and fifth week of the experiment for measurement of substrate oxidation rates, energy expenditure, activity, and food intake. Mice were killed after 6 weeks of treatment. Initiation of treatment with AMP-DNM resulted in a rapid increase in fat oxidation by 129% (P = .05), a decrease in carbohydrate oxidation by 35% (P = .01), and a reduction in food intake by approximately 26% (P < .01) compared with control mice. Treatment with AMP-DNM decreased hepatic triglyceride content by 66% (P < .01) and, in line with the elevated fat oxidation rates, increased hepatic carnitine palmitoyl transferase 1a expression. Treatment with AMP-DNM increased plasma levels of the appetite-regulating peptide YY compared with control mice. Treatment with AMP-DNM rapidly reduces food intake and increases fat oxidation, resulting in improvement of the obese phenotype. These features of AMP-DNM, together with its insulin-sensitizing capacity, make it an attractive candidate drug for the treatment of obesity and its associated metabolic derangements.

Topics: 1-Deoxynojirimycin; Adamantane; Adipose Tissue; Animals; Body Weight; Carbohydrate Metabolism; Carnitine O-Palmitoyltransferase; Eating; Ghrelin; Glucose; Imino Sugars; Liver; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Oxidation-Reduction; Peptide YY; Triglycerides; Up-Regulation; Weight Gain

Ileal interposition (IT), in which the distal ileum is transposed isoperistaltically into the proximal jejunum, is considered as a procedure for metabolic or antidiabetes surgery. Our aim was to study the effects of IT on glycemic control, fat metabolism, and hormonal changes in obese rats with spontaneous diabetes.. Animals were divided into either an IT or a sham (SH) group. They underwent an oral glucose tolerance test (OGTT) before and 4 and 8 weeks after the operation. All animals were killed 10 weeks after operation for analyses of tissue weight (liver, pancreas, epididymal fat, brown fat), immunoblotting of uncoupling protein-1 (UCP1) protein in brown adipose tissue (BAT), and fasting plasma levels of glucose, insulin, glucagon-like peptide (GLP)-1, peptide YY (PYY), glucose-dependent insulinotropic polypeptide (GIP), and leptin.. Body weight increased postoperatively in both groups compared with preoperative weight, but it did not differ between the 2 groups. Eight weeks postoperatively, integrated blood glucose levels during the OGTT were decreased in IT compared with SH (P < .05). Fasting plasma levels of insulin, GLP-1, and GIP did not differ between the 2 groups, but PYY levels were higher in the IT animals (P < .01). The weight of epididymal and BATs, homeostasis model assessment insulin resistance, and fasting plasma leptin levels were decreased in the IT group (P < .05). Expression of UCP1 was higher in IT than SH animals (P < .05).. These results suggest that IT improves glucose and lipid metabolism by decreasing insulin resistance and epididymal fat, and increased expression of UCP1 in BAT might be among the mechanisms responsible.

Topics: Adipose Tissue, Brown; Animals; Body Weight; Comorbidity; Diabetes Mellitus; Disease Models, Animal; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucose; Ileum; Insulin Resistance; Ion Channels; Jejunum; Leptin; Lipid Metabolism; Male; Mitochondrial Proteins; Obesity; Peptide YY; Rats, Inbred OLETF; Uncoupling Protein 1

The objective was to elucidate the relationships between serum concentrations of the gut hormone peptide YY (PYY) and ghrelin and growth development in infants for potential application to the clinical observation index. Serum concentrations of PYY and ghrelin were measured using radioimmunoassay from samples collected at the clinic. For each patient, gestational age, birth weight, time required to return to birth weight, rate of weight gain, time required to achieve recommended daily intake (RDI) standards, time required for full-gastric feeding, duration of hospitalization, and time of administration of total parenteral nutrition were recorded. Serum PYY and ghrelin concentrations were significantly higher in the preterm group (N = 20) than in the full-term group (N = 20; P < 0.01). Within the preterm infant group, the serum concentrations of PYY and ghrelin on postnatal day (PND) 7 (ghrelin = 1485.38 ± 409.24; PYY = 812.37 ± 153.77 ng/L) were significantly higher than on PND 1 (ghrelin = 956.85 ± 223.09; PYY = 545.27 ± 204.51 ng/L) or PND 3 (ghrelin = 1108.44 ± 351.36; PYY = 628.96 ± 235.63 ng/L; P < 0.01). Both serum PYY and ghrelin concentrations were negatively correlated with body weight, and the degree of correlation varied with age. Serum ghrelin concentration correlated negatively with birth weight and positively with the time required to achieve RDI (P < 0.05). In conclusion, serum PYY and ghrelin concentrations reflect a negative energy balance, predict postnatal growth, and enable compensation. Further studies are required to elucidate the precise concentration and roles of PYY and ghrelin in newborns and to determine the usefulness of measuring these hormones in clinical practice.

Topics: Body Weight; Case-Control Studies; Energy Intake; Female; Ghrelin; Humans; Infant, Newborn; Infant, Premature; Male; Nutritional Requirements; Peptide YY; Radioimmunoassay; Weight Gain

Peptide YY (PYY) is best known for its important role in appetite regulation, but recent pharmacological studies have suggested that PYY is also involved in regulating energy balance and glucose homeostasis. However, the mechanism behind the regulation of these parameters by PYY is less clear. Here, by utilising an inducible transgenic mouse model where PYY overexpression is induced in adult animals (PYYtg) and release of mature PYY peptides is controlled by endogenous machineries, we show that elevating PYY levels leads to reduced food intake after a 24-h fast. Furthermore, PYYtg mice, although not significantly different from WT with respect to body weight, adiposity, lean mass, physical activity or energy expenditure, exhibited a significantly increased respiratory exchange ratio (RER), indicating decreased lipid oxidation and/or increased lipogenesis. Importantly, PYYtg mice showed a 25% reduction in liver protein levels of phosphorylated acetyl-CoA carboxylase (pACC) in the absence of changes in total ACC levels compared to those of WT mice. Moreover, liver protein levels of AMP-activated kinase (AMPK) in PYYtg mice were 25% lower than those of WT mice, consistent with a reduced pACC in these mice. These data suggest that elevation of PYY levels as seen after a meal can increase lipogenic capacity, which is likely a key contributor to the increased RER seen in PYYtg mice. In addition, PYYtg mice exhibited comparable insulin tolerance and oral glucose tolerance to those of WT, but showed a trend towards decreased insulin levels in response to an oral glucose challenge, indicating that PYY could improve insulin action. Taken together, these findings demonstrate that under physiological conditions, PYY reduces food intake while enhancing lipogenic capacity and insulin action, likely contributing to fuel assimilation in the postprandial state.

Topics: Acetyl-CoA Carboxylase; Animals; Animals, Genetically Modified; Body Weight; Eating; Fasting; Glucose Tolerance Test; Homeostasis; Lipid Metabolism; Male; Mice; Obesity; Peptide YY

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

Dietary conjugated linoleic acid (CLA) causes reduced feed intake (FI) and body fat (BF). It is unknown, though, if CLA incorporation into tissues, alterations in serum hormones, and/or appetite-regulating neuropeptides are involved. We hypothesized that CLA incorporation into brain lipids would be correlated with changes in appetite-regulating neuropeptide expression and reductions in FI and BF. Male mice (n = 150; 9 weeks old, ICR) received the control diet ad libitum (CON), 2% CLA diet ad libitum (CLA), or control diet pair-fed to the intake of CLA-fed mice for 1, 2, 3, 5, or 7 days. Both FI and body weight were measured daily, and a BF index was calculated. Liver, adipose, and brain fatty acids; serum insulin, leptin, and peptide YY; and arcuate nucleus neuropeptide Y, agouti-related protein, and α-melanocyte-stimulating hormone protein were determined. Mice fed CLA ate less (P < .05) than did the CON on days 1, 2, 3, and 7 but were leaner (P < .05) only on day 7. Mice that received the control diet pair-fed to the intake of CLA-fed mice did not differ in BF from the CON. By days 1 and 2, CLA isomers were incorporated into the liver and adipose but not in the brain. Insulin was increased in CLA-fed mice on days 5 and 7, and leptin was decreased on day 7. Peptide YY and the neuropeptides did not differ. Tissue CLA was not correlated with FI, body weight, or BF but was positively correlated with insulin and negatively correlated with leptin. The reduction in FI is not sufficient to cause the reduction in BF, and tissue CLA accumulation does not appear to be required.

Topics: Adipose Tissue; Animals; Anti-Obesity Agents; Appetite Regulation; Body Weight; Brain; Diet; Dietary Fats; Energy Intake; Feeding Behavior; Insulin; Leptin; Linoleic Acids, Conjugated; Liver; Mice; Mice, Inbred ICR; Neuropeptides; Peptide YY

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

This study investigated the effects of peripheral administration of ghrelin and PYY(3-36) on food intake and plasma and tissue fasting and postprandial ghrelin and PYY(3-36) levels in normal-weight (NW) and diet-induced-obese (DIO) rats.. In experiment one, NW and DIO rats received a single intraperitoneal injection of saline, PYY(3-36) or ghrelin; food intake was measured for 4 h. In experiment two, total plasma ghrelin and PYY(3-36), gastric fundus ghrelin, and ascending colon PYY(3-36) were measured either after a 20-h fast or 2 h after refeeding in NW and DIO rats by radioimmunoassay.. Compared to the NW rats, findings in the DIO rats revealed: (i) a reduced sensitivity to both the anorectic effect of exogenous PYY(3-36) and the orexigenic effect of exogenous ghrelin; (ii) the postprandial plasma ghrelin levels were significantly higher; and (iii) refeeding decreased endogenous plasma ghrelin levels by 53% in the NW rats and 39% in DIO rats. Refeeding increased the plasma PYY(3-36) level by 58% in the NW rats versus 9% in the DIO rats (P=0.003).. Compared with regular rats, DIO rats exhibit blunted responses in food intake to exogenous ghrelin and PYY(3-36). Although endogenous ghrelin and PYY(3-36) in DIO rats are not altered in the fasting state, their responses to food ingestion are blunted in comparison with regular rats.

Topics: Animals; Blood Glucose; Body Weight; Colon; Diet; Disease Models, Animal; Eating; Fasting; Gastric Fundus; Ghrelin; Injections, Intraperitoneal; Male; Obesity; Peptide Fragments; Peptide YY; Postprandial Period; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Time Factors

Intrauterine growth restriction (IUGR) is associated with a substantially greater incidence of metabolic syndrome in adulthood. Animal studies have shown that IUGR offspring are hyperphagic during the early postnatal period and therefore exhibit obesity. The molecular mechanisms underlying food intake regulation in the gastrointestinal tract have not been clarified in IUGR. In the present study, we utilized a rat model of IUGR by restricting the food intake of the mother (50% of the normal intake, ad libitum; FR group) from day 7 of gestation until delivery. Pups from undernourished mothers were fostered by control mothers. We examined the food intake and assessed the gene expressions of ghrelin, peptide YY (PYY), and cholecystokinin (CCK) in the alimentary tract of male newborns (postnatal day1) and adult offspring (age, 7 months). Compared to the offspring whose mothers received the standard diet ad libitum (CON offspring), FR offspring were hyperphagic from the weaning time until the end of the experiment, and resulted in a heavier final weight. Both newborn and adult FR offspring had higher ghrelin gene expression in the stomach and higher ghrelin plasma levels than did the controls. Although the gastrointestinal gene expressions and plasma levels of the anorexic peptides, PYY and CCK, were elevated in the FR newborns, they decreased in the FR adults. Our findings suggest that the altered gene expressions of orexigenic and anorexigenic gut peptides in the gastrointestinal tract in the maternal undernutrition-induced IUGR offspring provide a potential mechanism to explain hyperphagia and obesity seen in these offspring.

Topics: Adult; Animals; Animals, Newborn; Body Weight; Cholecystokinin; Disease Models, Animal; Eating; Female; Fetal Growth Retardation; Gastrointestinal Tract; Gene Expression; Gene Expression Regulation, Developmental; Ghrelin; Humans; Hyperphagia; Male; Peptide YY; Rats; Rats, Sprague-Dawley; Up-Regulation

PYY may play a role in modulating satiety and energy expenditure; increasing PYY postprandially has been studied largely in single-meal responses. The diurnal rhythm of PYY and its role in energy balance have not been fully characterized. The purpose of our study was to characterize features of the diurnal rhythm of PYY and determine its role in regulating energy balance. This study was a cross-sectional analysis of 11 subjects in whom 24-h repeated blood sampling was conducted at baseline of a larger prospective study. Breakfast (B), lunch (L), dinner (D), and a snack (S) occurred between 0900 and 1900. Total PYY was assayed every hour from 0800 to 1000, every 20 min from 1000 to 2000, and every hour from 2000 to 0800. PYY variables included total AUC, postprandial peaks, and 24-h mean. Energy balance variables included energy intake, RMR, RQ, and NEAT. PYY postprandial peaks were significantly higher than fasting (P < 0.05). Twenty-four-hour peak PYY occurred after L and was significantly higher than all other peaks (P < 0.05). A cubic curve function accounted for most of the variance in PYY (r(2) = 69.9%, P < 0.01). Fasting PYY (0800) correlated with postprandial peaks at B (r = 0.77, P = 0.01), L (r = 0.71, P = 0.01), and D (r = 0.65, P = 0.03). The only significant association between PYY and energy expenditure was that RMR (kcal/24 h) correlated with 24-h mean PYY (r = 0.71, P = 0.013) and total AUC (r = 0.69, P = 0.019). We conclude that PYY displays a meal-driven diurnal rhythm and is correlated to RMR, a major contributor to energy expenditure. Thus, PYY varies in accordance with energy content and RMR, supporting a role for PYY in energy balance modulation.

Topics: Adolescent; Basal Metabolism; Body Weight; Circadian Rhythm; Energy Metabolism; Female; Humans; Peptide YY; Premenopause; Satiety Response; Young Adult

This study tested the effects of (1→3),(1→4) β-D-glucan from oats, on activation of the gut-hypothalamic (PYY₃₋₃₆-NPY) axis, satiety, and weight loss in diet-induced obesity (DIO) mice. DIO mice were fed standard lab chow diets or varied doses of β-glucan for 6 weeks. Energy intake, satiety, body weight changes and peptide Y-Y₃₋₃₆ (PYY₃₋₃₆) were measured together with a satiety test and measurement of neuropeptide Y (NPY) mRNA expression in the hypothalamic arcuate nucleus (Arc). The average energy intake (-13%, p<0.05) and body weight gain was lower with increasing β-glucan over 6 wk with acute suppression of energy intake over 4 h. The highest β-glucan diet significantly increased plasma PYY₃₋₃₆, with suppression of Arc NPY mRNA.

Topics: Animals; Arcuate Nucleus of Hypothalamus; Avena; beta-Glucans; Body Weight; Diet; Dose-Response Relationship, Drug; Energy Intake; Gastrointestinal Tract; Male; Mice; Mice, Inbred C57BL; Neuropeptide Y; Obesity; Peptide Fragments; Peptide YY; RNA, Messenger; Satiety Response

Apolipoprotein A-IV (apoA-IV) is synthesized by intestinal enterocytes during lipid absorption and secreted into lymph on the surface of nascent chylomicrons. A compelling body of evidence supports a central role of apoA-IV in facilitating intestinal lipid absorption and in regulating satiety, yet a longstanding conundrum is that no abnormalities in fat absorption, feeding behavior, or weight gain were observed in chow-fed apoA-IV knockout (A4KO) mice. Herein we reevaluated the impact of apoA-IV expression in C57BL6 and A4KO mice fed a high-fat diet. Fat balance and lymph cannulation studies found no effect of intestinal apoA-IV gene expression on the efficiency of fatty acid absorption, but gut sac transport studies revealed that apoA-IV differentially modulates lipid transport and the number and size of secreted triglyceride-rich lipoproteins in different anatomic regions of the small bowel. ApoA-IV gene deletion increased expression of other genes involved in chylomicron assembly, impaired the ability of A4KO mice to gain weight and increase adipose tissue mass, and increased the distal gut hormone response to a high-fat diet. Together these findings suggest that apoA-IV may play a unique role in integrating feeding behavior, intestinal lipid absorption, and energy storage.

Topics: Adipose Tissue; Animals; Apolipoproteins A; Biological Transport; Body Weight; Catheterization; Diet, High-Fat; Dietary Fats; Eating; Gene Expression Regulation; Gene Knockout Techniques; Glucagon-Like Peptide 1; Growth and Development; Intestinal Mucosa; Lipid Metabolism; Lymphatic Vessels; Male; Mice; Mice, Inbred C57BL; Particle Size; Peptide YY; Triglycerides

We hypothesized that soy protein (S)-based diets fed during pregnancy and lactation increase food intake and the presence of characteristics of the metabolic syndrome to a lesser extent in female than in male rats. Soy protein- and casein (C)-based American Institute of Nutrition-93G diets were fed to 2 groups (n = 12 per group) of pregnant Wistar rats from day 3 of gestation and throughout lactation. Their effects on characteristics of metabolic syndrome and food intake regulation in female pups maintained for 15 weeks on the C diet were compared. Body weight (BW) and food intake (FI) were measured weekly. Fat pad mass was measured at birth, at weaning, and at week 15. Glucose and insulin tolerance tests were conducted at weeks 8 and 12; and systolic and diastolic blood pressures were measured at weeks 4, 8, and 12. Plasma was collected at weaning and at the end of the studies for glucose, insulin, glucagon-like peptide 1, peptide YY, and ghrelin. Food intake in response to protein preloads was measured at week 7. Feeding the S diet throughout gestation and lactation resulted in higher systolic blood pressure (P < .005), FI (P < .05), and glucagon-like peptide 1 and lower peptide YY at weaning and higher BW during weeks 11 to 15 and fat pad mass at week 15 (all Ps < .05). However, no sign of insulin resistance was found; nor was short-term FI in response to protein preloads affected. In conclusion, S- compared with C-based American Institute of Nutrition-93 G diets consumed throughout gestation and lactation increased BW and FI later and resulted in fewer characteristics of metabolic syndrome in female than in male offspring.

Topics: Adipose Tissue; Animals; Biomarkers; Blood Pressure; Body Weight; Caseins; Diet; Dietary Proteins; Energy Intake; Female; Glucagon-Like Peptide 1; Humans; Lactation; Male; Metabolic Syndrome; Peptide YY; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Sex Factors; Soybean Proteins

Peptide YY(3-36) is a satiation hormone released postprandially into the bloodstream from L-endocrine cells in the gut epithelia. In the current report, we demonstrate PYY(3-36) is also present in murine as well as in human saliva. In mice, salivary PYY(3-36) derives from plasma and is also synthesized in the taste cells in taste buds of the tongue. Moreover, the cognate receptor Y2R is abundantly expressed in the basal layer of the progenitor cells of the tongue epithelia and von Ebner's gland. The acute augmentation of salivary PYY(3-36) induced stronger satiation as demonstrated in feeding behavioral studies. The effect is mediated through the activation of the specific Y2 receptor expressed in the lingual epithelial cells. In a long-term study involving diet-induced obese (DIO) mice, a sustained increase in PYY(3-36) was achieved using viral vector-mediated gene delivery targeting salivary glands. The chronic increase in salivary PYY(3-36) resulted in a significant long-term reduction in food intake (FI) and body weight (BW). Thus this study provides evidence for new functions of the previously characterized gut peptide PYY(3-36) suggesting a potential simple and efficient alternative therapeutic approach for the treatment of obesity.

Topics: Administration, Oral; Adolescent; Adult; Animals; Body Weight; Eating; Epithelial Cells; Feeding Behavior; Gene Expression Regulation; Humans; Mice; Peptide Fragments; Peptide YY; Saliva; Satiety Response; Time Factors; Tongue; Young Adult

Black women suffer a disproportionately higher rate of obesity than their white counterparts. Reasons for this racial disparity may reflect underlying differences in the appetite suppressing peptide-YY (PYY). The PYY response to food is differentially influenced by macronutrient content but the effect of glycemic load on PYY response is unknown. This study examined whether glycemic load influences fasting and postprandial PYY levels and whether fasting and postprandial PYY levels are lower in obese black women compared to normal weight black women and to white women. Data were collected from 40 women (20 black, 20 white; 10 each normal weight vs. obese) at the University of North Carolina Clinical and Translational Research Center (CTRC). Participants completed in counterbalanced order two 4(1/2)-day weight-maintenance, mixed macronutrient high vs. low glycemic load diets followed by a test meal of identical composition. Total PYY levels were assessed before and after each test meal. Results show no differences in fasting PYY levels but significantly less postprandial PYY area under the curve (PYY(AUC)) in the group of obese black women compared to each other group (race x obesity interaction, P < 0.04). PYY(AUC) was positively related to insulin sensitivity (P < 0.004) but was not affected by glycemic load (main and interactive effects, P > 0.27). These findings indicate that postprandial PYY secretion is not affected by glycemic load but is blunted in obese black women compared with normal weight black women and with white women; additionally, they begin to address whether blunted PYY secretion contributes uniquely to the pathogenesis of obesity in black women.

Topics: Adult; Black People; Body Weight; Eating; Fasting; Female; Humans; Hyperglycemia; Insulin Resistance; Obesity; Peptide YY; Prevalence; United States; White People; Young Adult

Epidemiologic studies suggest that childbearing is an important contributor to the development of obesity in many women and that breastfeeding may be protective. Ghrelin and peptide YY (PYY) are gut hormones involved in appetite regulation and energy homeostasis and are biological neuroendocrine signals that potentially affect body weight and adiposity.. This study evaluated whether fasting or postprandial ghrelin or PYY is different between lactating and nonlactating postpartum women matched for age, body weight, and adiposity.. Ten postpartum lactating women (mean + or - SD: 28.1 + or - 4.9 y of age, 69.2 + or - 11.3 kg, 35.4 + or - 6.6% body fat) and 8 nonlactating women (28.8 + or - 7.6 y of age, 75.6 + or - 13.7 kg, 37.5 + or - 6.5% body fat) at 4-5 wk postpartum underwent measurements of body weight, body composition, and ghrelin and PYY responses to a standardized meal (350 kcal). Seven never-pregnant women served as control subjects (29.7 + or - 4.1 y of age, 60.4 + or - 4.8 kg, 25.5 + or - 2.0% body fat).. Ghrelin concentrations decreased, whereas PYY concentrations increased significantly (P < 0.05) in response to the meal, but fasting or meal-induced changes were not significantly different between lactating and nonlactating women. The fasting ghrelin concentration correlated with body mass index (r = -0.53, P < 0.05) and was significantly lower in postpartum than in control women (894.9 + or - 247.7 compared with 1316.9 + or - 241.0 pg/mL), even after adjustment for body mass index.. Our data do not support the notion that ghrelin, PYY, or both are plausible neuroendocrine signals that influence body weight regulation during lactation. They suggest, however, that ghrelin may change with increased adiposity in the postpartum state and may potentially play a role in body weight regulation after child birth.

Topics: Adult; Basal Metabolism; Body Composition; Body Mass Index; Body Weight; Calorimetry, Indirect; Female; Ghrelin; Humans; Lactation; Longitudinal Studies; Peptide YY; Postpartum Period

Intestinal nutrient infusions result in variable decreases in food intake and body weight based on the nutrient type and the specific intestinal infusion site. Only intrajejunal infusions of fatty acids decrease food intake beyond the calories infused. To test whether this extra-compensatory decrease in food intake is specific to fatty acids, small volume intrajejunal infusions of glucose (Glu) and casein hydrolysate (Cas), as well as linoleic acid (LA) were administered to male Sprague-Dawley rats. Equal kilocalorie (kcal) loads of these nutrients (11.4) or vehicle were infused into the jejunum over 7 h/day for five consecutive days. Food intake was continuously monitored and body weight was measured daily. After the infusion on the final day, rats were killed and plasma collected. Intrajejunal infusions of LA and Glu, but not Cas, suppressed food intake beyond the caloric load of the infusate with no compensatory increase in food intake after the infusion period. Rats receiving LA and Glu infusions also lost significant body weight across the infusion days. Plasma glucagon-like peptide-1 (GLP-1) was increased in both the LA and Glu rats compared with control animals, with no significant change in the Cas-infused animals. Peptide YY (PYY) levels increased in response to LA and Cas infusions. These results suggest that intrajejunal infusions of LA and Glu may decrease food intake and body weight via alterations in GLP-1 signaling. Thus, particular nutrients are more effective at producing decreases in food intake, body weight, and inducing changes in peptide levels and could lead to a novel therapy for obesity.

Topics: Analysis of Variance; Animals; Body Weight; Caseins; Eating; Energy Intake; Enzyme-Linked Immunosorbent Assay; Glucagon-Like Peptide 1; Glucose; Jejunum; Leptin; Linoleic Acid; Male; Peptide YY; Radioimmunoassay; Rats; Rats, Sprague-Dawley

Roux-en-Y gastric bypass (RYGB) surgery is the most effective treatment for morbid obesity and remission of associated type 2 diabetes, but the mechanisms involved are poorly understood. The aim of the present study was to develop and validate a rat model for RYGB surgery that allows repeated measurement of meal-induced changes in gut and pancreatic hormones via chronic venous catheters. Male Sprague Dawley rats made obese on a palatable high-fat diet were subjected to RYGB or sham surgery and compared with chow-fed, lean controls. Hormonal responses to a mixed-liquid test meal were examined by frequent blood sampling through chronically implanted jugular catheters in freely behaving rats, 3-4 months after surgery, when RYGB rats had significantly reduced body weight and fat mass compared with sham-operated rats. Hyperleptinemia, basal hyperinsulinemia, and hyperglycemia as well as postprandial glucose intolerance seen in sham-operated, obese rats were completely reversed by RYGB and no longer different from lean controls. Postprandial increases in glucagon-like peptide-1, peptide YY, and amylin as well as suppression of ghrelin levels were all significantly augmented in RYGB rats compared with both sham-operated obese and lean control rats. Thus, our rat model replicates most of the salient hormonal and glycemic changes reported in obese patients after RYGB, with the addition of amylin to the list of potential candidate hormones involved in hypophagia, weight loss, and remission of diabetes. The model will be useful for elucidating the specific peripheral and central mechanisms involved in the suppression of appetite, loss of body weight, and remission of type 2 diabetes.

Topics: Amyloid; Analysis of Variance; Animals; Body Weight; Eating; Gastric Bypass; Ghrelin; Glucagon-Like Peptide 1; Insulin; Islet Amyloid Polypeptide; Leptin; Male; Obesity; Peptide YY; Postprandial Period; Rats; Rats, Sprague-Dawley; Time Factors

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

The mechanism and routes through which peptide tyrosine-tyrosine (PYY) exerts its anorectic effects are still largely unknown. In the present study, we investigated the roles of the area postrema (AP), subfornical organ (SFO) and vagus nerve in mediating the anorectic effect of PYY using PYY(3-36) conjugated to human serum albumin (PYY(3-36)-HSA) in rats. PYY(3-36)-HSA is a large molecule that does not penetrate the blood-brain barrier, and thus provides a useful tool to discriminate between the central (brain) and peripheral actions of this peptide. PYY(3-36)-HSA induced significant reductions in food and body weight gain up to 24 h after administration. The anorectic effect of PYY(3-36)-HSA was delayed for 2 h in rats in which both AP and SFO were ablated, while lesion of either of these circumventricular organs in isolation did not influence the feeding responses to PYY(3-36)-HSA. The PYY(3-36)-HSA-induced anorectic effect was also reduced during the 3- to 6-h period following subdiaphragmatic vagotomy. Lesions of AP, SFO and AP/SFO as well as subdiaphragmatic vagotomy blunted PYY(3-36)-HSA-induced expression of c-fos mRNA in specific brain structures including the bed nucleus of stria terminalis, central amygdala, lateral-external parabrachial nucleus and medial nucleus of the solitary tract. In addition, subdiaphragmatic vagotomy inhibited the neuronal activation induced by PYY(3-36)-HSA in AP and SFO. These findings suggest that the anorectic effect and brain neuronal activation induced by PYY(3-36)-HSA are dependent on integrity of AP, SFO and subdiaphragmatic vagus nerve.

Topics: Animals; Appetite Depressants; Appetite Regulation; Area Postrema; Blood Glucose; Body Weight; Brain; Drinking; Eating; Humans; Insulin; Male; Neurons; Peptide Fragments; Peptide YY; Rats; Rats, Wistar; Serum Albumin; Subfornical Organ; Vagotomy; Vagus Nerve

Potential implications of gut hormones in body mass and torpor and behavioral pattern changes induced by an incremental (40 and 80%) calorie restriction (CR) in long-days (LD, summer) and short-days (SD, winter) were investigated in gray mouse lemurs. Only 80% food-deprived LD and SD animals showed a continuous mass loss resulting in a 10 and 15% mass reduction, respectively. Ghrelin levels of all food-deprived groups increased by 2.6-fold on average and remained high after re-feeding while peptide YY (PYY) levels increased by 3.8-fold only in LD animals under 80% CR. In the re-fed SD group, body mass was positively associated with ghrelin and negatively associated with PYY, while no correlations were noted in the re-fed LD animals. Plasma glucagon-like peptide-1 (GLP-1) increased by 2.9-fold only in LD food-restricted mouse lemurs and was negatively associated with the minimal body temperature. No significant correlations were reported in food-deprived SD animals. These results suggest that ghrelin, PYY and GLP-1 may be related to pre-wintering fattening mechanisms and to the modulation of torpor expression, respectively. Such observation clearly warrants further investigations, but it opens an interesting area of research in torpor regulation.

Topics: Adaptation, Physiological; Animals; Behavior, Animal; Body Temperature; Body Weight; Cheirogaleidae; Eating; Food Deprivation; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Hypothermia; Motor Activity; Peptide YY; Seasons

Resistant starch (RS) is fermentable dietary fiber. Inclusion of RS in the diet causes decreased body fat accumulation and altered gut hormone profile. This study investigates the effect of feeding RS on the neuropeptide messenger RNA (mRNA) expressions in the arcuate nucleus (ARC) of the hypothalamus and whether vagal afferent nerves are involved. The rats were injected intraperitoneally with capsaicin to destroy unmyelinated small vagal afferent nerve fibers. The cholecystokinin (CCK) food suppression test was performed to validate the effectiveness of the capsaicin treatment. Then, capsaicin-treated rats and vehicle-treated rats were subdivided into a control diet or a RS diet group, and fed the corresponding diet for 65 days. At the end of study, body fat, food intake, plasma peptide YY (PYY) and glucagon-like peptide 1 (GLP-1), and hypothalamic pro-opiomelanocortin (POMC), neuropeptide Y (NPY), agouti-related peptide (AgRP) gene expressions were measured. RS-fed rats had decreased body fat, increased POMC expression in the hypothalamic ARC, and elevated plasma PYY and GLP-1 in both the capsaicin and vehicle-treated rats. Hypothalamic NPY and AgRP gene expressions were not changed by RS or capsaicin. Therefore, destruction of the capsaicin-sensitive afferent nerves did not alter the response to RS in rats. These findings suggest that dietary RS might reduce body fat through increasing the hypothalamic POMC expression and vagal afferent nerves are not involved in this process. This is the first study to show that dietary RS can alter hypothalamic POMC expression.

Topics: Agouti-Related Protein; Animal Feed; Animals; Body Weight; Capsaicin; Cholecystokinin; Dietary Fiber; Energy Intake; Gene Expression Regulation; Glucagon-Like Peptide 1; Hypothalamus; Male; Peptide YY; Pro-Opiomelanocortin; Rats; Rats, Sprague-Dawley

Gut hormones represent attractive therapeutic targets for the treatment of obesity and type 2 diabetes. However, controversy surrounds the effects that adiposity, dietary manipulations, and bariatric surgery have on their circulating concentrations. We sought to determine whether these discrepancies are due to methodologic differences.. Ten normal-weight males participated in a 4-way crossover study investigating whether fasting appetite scores, plasma acyl-ghrelin, active glucagon-like peptide-1 (GLP-1), and peptide YY3-36 (PYY3-36) levels are altered by study-induced stress, prior food consumption, and sample processing.. Study visit order affected anxiety, plasma cortisol, and temporal profiles of appetite and plasma PYY3-36, with increased anxiety and cortisol concentrations on the first study day. Plasma cortisol area under the curve (AUC) correlated positively with plasma PYY3-36 AUC. Despite a 14-hour fast, baseline hunger, PYY3-36 concentrations, temporal appetite profiles, PYY3-36 AUC, and active GLP-1 were affected by the previous evening's meal. Sample processing studies revealed that sample acidification and esterase inhibition are required when measuring acyl-ghrelin and dipeptidyl-peptidase IV inhibitor addition for active GLP-1. However, plasma PYY3-36 concentrations were unaffected by addition of dipeptidyl-peptidase IV.. Accurate assessment of appetite, feeding behavior, and gut hormone concentrations requires standardization of prior food consumption and subject acclimatization to the study protocol. Moreover, because of the labile nature of acyl-ghrelin and active GLP-1, specialized sample processing needs to be undertaken.

Topics: Adaptation, Psychological; Adult; Analysis of Variance; Appetite; Area Under Curve; Body Weight; Cross-Over Studies; Feeding Behavior; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Hunger; Hydrocortisone; Male; Peptide YY; Probability; Reference Standards; Reference Values; Risk Factors; Sampling Studies; Sensitivity and Specificity; Stress, Psychological

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

In previous research, peptide YY (PYY) administered in supraphysiological doses did not induce significant proliferative effects in rats that were allowed to feed ad libitum after massive small bowel resection (SBR). The main reason may well have been the interference of endogenous PYY released from L cells in the distal bowel in response to the presence of augmented unabsorbed intraluminal nutrients. The purpose of the present study was to explore the effect of PYY on intestinal proliferation with total enteral nutrition (TEN) in a SBR model of PYY knockout (Pyy(-/-)) mice, which do not produce endogenous PYY.. Pyy(-/-) mice were assigned into 3 experimental groups: sham mice (sham group) underwent bowel transection and reanastomosis, and received TEN; SBR mice (SBR group) underwent a 50% small bowel resection, and received TEN; and SBR-PYY mice (SBR-PYY group) underwent a 50% small bowel resection, received TEN, and were treated with PYY1-36 subcutaneously from day 2 postoperatively. Parameters of enterocyte proliferation and apoptosis were determined on day 8 following operation.. SBR-PYY mice demonstrated a significant increase in (vs SBR) bowel and mucosal weights, mucosal DNA and protein, villus height, and crypt depth in jejunum and ileum. SBR-PYY mice also showed an increased crypt cell proliferation index in jejunum and ileum and decreased villus cell apoptotic index in ileum compared with SBR animals.. In an SBR model of Pyy(-/-) mice, PYY induces proliferation of residual intestine with TEN.

Topics: Animals; Apoptosis; Body Weight; Cell Proliferation; DNA; Enteral Nutrition; Ileum; Intestinal Mucosa; Jejunum; Male; Mice; Mice, Knockout; Organ Size; Peptide YY; Proteins

Neuropeptide Y (NPY) and its family of peptides are thought to have a major role in the physiological control of energy homeostasis. Among five NPY receptors described, stimulation of the Y2 receptor (Y2R) or inhibition of the Y5 receptor (Y5R) has recently been shown to produce weight-lowering effects in obese rodents. The present study examined and compared the effects of a Y2R agonist, PYY(3-36), and a Y5R antagonist, alone and in combination, on food intake and body weight in diet-induced obese (DIO) mice. Acute intraperitoneal injection of PYY(3-36) dose-dependently reduced spontaneous feeding in lean and DIO mice. In contrast, acute oral administration of the Y5R antagonist had no effect on spontaneous feeding or the anorexigenic effects of PYY(3-36). In a chronic study, subcutaneous infusion of PYY(3-36) (1 mg/kg/day for 14 days) significantly reduced food intake and body weight in DIO mice. The Y5R antagonist (10 mg/kg/day for 14 days, orally) reduced body weight to the same extent as PYY(3-36) without a significant feeding reduction. Combined administration of PYY(3-36) and the Y5R antagonist resulted in a greater body weight reduction than treatment with either agent alone. The combined effects on food intake, body weight, and adiposity are almost the same as a hypothetical sum of the effects of each drug alone. These results illustrate that the combination of a Y2R agonist, PYY(3-36), and a Y5R antagonist resulted in additive effects on body weight and adiposity in DIO mice, suggesting that Y2R stimulation signal and Y5R blockade signal act by distinct pathways.

Topics: Adiposity; Animals; Anti-Obesity Agents; Body Weight; Dietary Fats; Eating; Male; Mice; Mice, Inbred C57BL; Obesity; Peptide YY; Receptors, Neuropeptide Y

Peptide YY (PYY) and neuropeptide Y (NPY) have been proposed to participate in the control of energy homeostasis. Since these activities show circadian variations, we explored the circadian pattern of locomotor, exploratory and ingestive behaviour in male and/or female mice with disrupted genes for PYY (PYY-/-), NPY (NPY-/-) as well as PYY plus NPY (PYY+NPY-/-). The effect of bacterial lipopolysaccharide (LPS, 0.1 mg/kg intraperitoneally) on these behaviours was also examined. The animals were housed singly in cages fitted with sensors for water and food intake and two infrared frames for recording ambulation and rearing under a 12 h light/dark cycle for 4 days. Locomotor and exploratory behaviour was decreased in female NPY-/- as well as male and female PYY+NPY-/- mice during the photo- and scotophase, and in male PYY-/- mice during the scotophase. Significant decreases in water and food intake were seen in female NPY-/- as well as male and female PYY+NPY-/- mice during the photophase. The effect of LPS to attenuate ingestive behaviour during the light and/or dark phase was most pronounced in PYY-/- and NPY-/- mice. These findings attest to a circadian cycle- and gender-related role of NPY and PYY in the control of behaviours that balance energy intake and energy expenditure. Both peptides stimulate feeding and drinking to balance the energy demand that they generate by enforcing the circadian pattern of locomotion and exploration. In addition, they counteract the anorectic and antidipsogenic effects of immune challenge.

Topics: Analysis of Variance; Animals; Behavior, Animal; Body Weight; Central Nervous System Agents; Circadian Rhythm; Drinking; Eating; Exploratory Behavior; Feeding Behavior; Female; Lipopolysaccharides; Male; Mice; Mice, Knockout; Motor Activity; Neuropeptide Y; Peptide YY; Sex Characteristics; Time Factors

Chronic administration of anorexigenic substances to experimental animals by injections or continuous infusion typically produces either no effect or a transient reduction in food intake and body weight. Our aim here was to identify an intermittent dosing strategy for intraperitoneal infusion of peptide YY(3-36) [PYY(3-36)] that produces a sustained reduction in daily food intake and adiposity in diet-induced obese rats. Rats (665+/-10 g body wt, 166+/-7 g body fat) with intraperitoneal catheters tethered to infusion swivels had free access to a high-fat diet. Vehicle-treated rats (n=23) had relatively stable food intake, body weight, and adiposity during the 9-wk test period. None of 15 PYY(3-36) dosing regimens administered in succession to a second group of rats (n=22) produced a sustained 15-25% reduction in daily food intake for >5 days, although body weight and adiposity were reduced across the 9-wk period by 12% (594+/-15 vs. 672+/-15 g) and 43% (96+/-7 vs. 169+/-9 g), respectively. The declining inhibitory effect of PYY(3-36) on daily food intake when the interinfusion interval was >or=3 h appeared to be due in part to an increase in food intake between infusions. The declining inhibitory effect of PYY(3-36) on daily food intake when the interinfusion interval was <3 h suggested possible receptor downregulation and tolerance to frequent PYY(3-36) administration; however, food intake significantly increased when PYY(3-36) treatments were discontinued for 1 day following apparent loss in treatment efficacies. Together, these results demonstrate the development of a potent homeostatic response to increase food intake when PYY(3-36) reduces food intake and energy reserves in diet-induced obese rats.

Topics: Adiposity; Animals; Appetite Depressants; Behavior, Animal; Body Weight; Dietary Fats; Disease Models, Animal; Drug Administration Schedule; Eating; Homeostasis; Infusions, Parenteral; Male; Obesity; Peptide Fragments; Peptide YY; Rats; Rats, Sprague-Dawley; Time Factors

In the Western world, consumption of soft drinks has increased the last three decades and is partly responsible for the epidemic-like increase in obesity. Soft drinks, originally sweetened by sucrose, are now sweetened by other caloric sweeteners, such as fructose. In this study, we investigated the short-term effect of sucrose, glucose or fructose solutions on food intake and body weight in rats, and on peripheral and central appetite signals. Rats received water containing either of the sugars and standard rat chow for two weeks. Rats receiving water alone and standard chow were controls. All rats offered the sugar solutions increased their total caloric intake. The increased caloric intake occurred despite the fact that the rats offered either of the sugar solutions consumed less chow. As a consequence of the increased caloric intake, the sugar-drinking rats had elevated serum levels of free fatty acids, triglycerides and cholesterol. In addition, consuming sugar solutions resulted in increased serum leptin, decreased serum PYY and down-regulated hypothalamic NPY mRNA. Serum ghrelin was increased in rats receiving fructose solution. Moreover, consumption of sucrose or fructose solution resulted in up-regulated hypothalamic CB1 mRNA. Hypothalamic POMC mRNA was down-regulated in rats receiving glucose or fructose. In conclusion, consumption of glucose, sucrose or fructose solution results in caloric overconsumption and body weight gain through activation of hunger signals and depression of satiety signals as well as activation of reward components. The weight-promoting effect of these sugar solutions may possibly be ameliorated by the down-regulation of NPY mRNA and increased serum leptin.

Topics: Administration, Oral; Animals; Appetite; Blood Glucose; Body Weight; Cholesterol; Dietary Carbohydrates; Eating; Energy Intake; Fatty Acids, Nonesterified; Female; Fructose; Gene Expression Regulation; Ghrelin; Glucose; Hypothalamus; Leptin; Neuropeptide Y; Peptide YY; Pro-Opiomelanocortin; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB1; RNA, Messenger; Solutions; Sucrose; Sweetening Agents; Triglycerides

Topics: Adult; Aged; Body Weight; Female; Ghrelin; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Peptide YY

The gut-derived hormone, peptide YY (PYY) reduces food intake and enhances satiety in both humans and animals. Obese individuals also have a deficiency in circulating peptide YY, although whether this is a cause or a consequence of obesity is unclear. Our aims were to determine whether peptide YY (PYY) over-expression may have therapeutic effects for the treatment of obesity by altering energy balance and glucose homeostasis. We generated PYY transgenic mice and measured body weight, food intake, temperature, adiposity, glucose tolerance, circulating hormone and lipid concentrations and hypothalamic neuropeptide levels (neuropeptide Y; proopiomelanocortin, and thyrotropin-releasing hormone) under chow and high-fat feeding and after crossing these mice onto the genetically obese leptin-deficient ob/ob mouse background. PYY transgenic mice were protected against diet-induced obesity in association with increased body temperature (indicative of increased thermogenesis) and sustained expression of thyrotropin-releasing hormone in the paraventricular nucleus of the hypothalamus. Moreover, PYY transgenic mice crossed onto the genetically obese ob/ob background had significantly decreased weight gain and adiposity, reduced serum triglyceride levels and improved glucose tolerance compared to ob/ob controls. There was no effect of PYY transgenic over expression on basal or fasting-induced food intake measured at 11-12 weeks of age. Together, these findings suggest that long-term administration of PYY, PYY-like compounds or agents that stimulate PYY synthesis in vivo can reduce excess adiposity and improve glucose tolerance, possibly via effects on the hypothalamo-pituitary-thyroid axis and thermogenesis.

Topics: Adiposity; Animals; Body Weight; Diet; Eating; Energy Metabolism; Glucose; Glucose Tolerance Test; Homeostasis; Hypothalamo-Hypophyseal System; In Situ Hybridization; Leptin; Mice; Mice, Inbred C57BL; Mice, Transgenic; Obesity; Paraventricular Hypothalamic Nucleus; Peptide YY; Reverse Transcriptase Polymerase Chain Reaction; Thermogenesis; Thyroid Gland; Thyrotropin

To characterize the gastrointestinal tract at the onset and in well-established obesity.. Lean (+/?) and obese (cp/cp) male JCR:LA-cp rats lacking a functional leptin receptor were killed at 3.5 weeks and 9 months of age and plasma concentrations of satiety hormones determined. The small intestine, colon, and stomach were measured, weighed, and mRNA levels of satiety genes quantified.. At the onset of obesity, obese rats had greater intestine, colon, and liver mass when adjusted for body weight compared to lean rats. Conversely, adult rats with established obesity had lower intestine and colon mass and length after adjustment for body weight. Early changes in gene expression included decreased ghrelin mRNA levels in stomach and increased peptide YY (PYY) mRNA levels in duodenum of young obese rats. After massive accumulation of adipose tissue had occurred, adult obese rats had increased proglucagon and ghrelin mRNA expression in the proximal intestine. In the distal small intestine, obese rats had lower proglucagon, ghrelin, and PYY mRNA levels. Finally, at the onset and in well-established obesity, obese rats had higher plasma insulin, amylin, glucagon like peptide-1 (GLP-1), and PYY, a finding, with the exception of insulin, unique to this model. Plasma total ghrelin levels were significantly lower at the onset of obesity and established obesity compared to the lean rats.. Several defects are manifested in the obese gut early on in the disease before the accumulation of large excesses of body fat and represent potential targets for early intervention in obesity.

Topics: Amyloid; Animals; Body Weight; Colon; Disease Models, Animal; Energy Metabolism; Female; Gastric Mucosa; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Insulin; Insulin Secretion; Intestine, Small; Islet Amyloid Polypeptide; Liver; Male; Obesity; Peptide YY; Proglucagon; Rats; Rats, Inbred Strains; RNA, Messenger; Satiety Response; Stomach

Functional changes induced by inflammation persist following recovery from the inflammatory response, but the mechanisms underlying these changes are not well understood. Our aim was to investigate whether the excitability and synaptic properties of submucosal neurons remained altered 8 wk post-trinitrobenzene sulfonic acid (TNBS) treatment and to determine whether these changes were accompanied by alterations in secretory function in submucosal preparations voltage clamped in Ussing chambers. Mucosal serotonin (5-HT) release measurements and 5-HT reuptake transporter (SERT) immunohistochemistry were also performed. Eight weeks after TNBS treatment, colonic inflammation resolved, as assessed macroscopically and by myeloperoxidase assay. However, fast excitatory postsynaptic potential (fEPSP) amplitude was significantly increased in submucosal S neurons from previously inflamed colons relative to those in control tissue. In addition, fEPSPs from previously inflamed colons had a hexamethonium-insensitive component that was not evident in age-matched controls. AH neurons were hyperexcitable, had shorter action potential durations, and decreased afterhyperpolarization 8 wk following TNBS adminstration. Neuronally mediated colonic secretory function was significantly reduced after TNBS treatment, although epithelial cell signaling, as measured by responsiveness to both forskolin and bethanecol in the presence of tetrodotoxin, was comparable with control tissue. 5-HT levels and SERT immunoreactivity were comparable to controls 8 wk after the induction of inflammation, but there was an increase in glucagon-like peptide 2-immunoreactive L cells. In conclusion, sustained alterations in enteric neural signaling occur following the resolution of colitis, which are accompanied by functional changes in the absence of active inflammation.

Topics: Action Potentials; Animals; Bethanechol; Body Weight; Cell Count; Colforsin; Colitis; Colon; Enteric Nervous System; Enteroendocrine Cells; Excitatory Postsynaptic Potentials; Glucagon-Like Peptide 2; Guinea Pigs; Male; Membrane Potentials; Neurons; Peptide YY; Peroxidase; Serotonin; Serotonin Plasma Membrane Transport Proteins; Submucous Plexus; Tetrodotoxin; Trinitrobenzenesulfonic Acid; Veratridine

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

Selective activation of the NPY2 receptor to suppress appetite provides an approach to obesity management. Selective NPY2 PEGylated peptide agonists are described that consist of a peptide core corresponding to residues 25-36 of PYY and a nonpeptidic moiety at the peptide N-terminus that contributes to in vitro potency and in vivo efficacy and provides a PEGylation site. The lead peptide elicits a dose-dependent reduction of food intake in lean mice and of food intake, body weight, and fat mass in DIO mice.

Topics: Animals; Anti-Obesity Agents; Body Weight; Cyclic AMP; Eating; Humans; Male; Mice; Mice, Inbred C57BL; Oligopeptides; Peptide Fragments; Peptide YY; Polyethylene Glycols; Radioligand Assay; Receptors, Neuropeptide Y; Structure-Activity Relationship

Peptide YY(3-36) [PYY(3-36)] is a gut-brain peptide that decreases food intake when administered by intravenous infusion to lean and obese humans and rats. However, chronic administration of PYY(3-36) by osmotic minipump to lean and obese rodents produces only a transient reduction in daily food intake and weight gain. It has recently been shown that 1-h intravenous infusions of PYY(3-36) every other hour for 10 days produced a sustained reduction in daily food intake, body weight, and adiposity in lean rats. Here, we determined whether intermittent delivery of PYY(3-36) can produce a similar response in diet-induced obese rats. During a 21-day period, obese rats (body fat >25%) received twice daily intraperitoneal infusion of vehicle (n = 18) or PYY(3-36) (n = 24) during hours 1-3 and 7-9 of the dark period. Rats had free access to both a 45% fat solid diet and a 29% fat liquid diet; intakes were determined from continuous computer recording of changes in food container weights. To sustain a 15-25% reduction in daily caloric intake, the initial PYY(3-36) dose of 30 pmol.kg(-1).min(-1) was reduced to 10 pmol.kg(-1).min(-1) on day 10 and then increased to 17 pmol.kg(-1).min(-1) on day 13. This dosing strategy produced a sustained reduction in daily caloric intake of 11-32% and prevented body weight gain (8 +/- 6 vs. 51 +/- 11 g) and fat deposition (4.4 +/- 7.6 vs. 41.0 +/- 12.8 g). These results indicate that intermittent intraperitoneal infusion of PYY(3-36) can produce a sustained reduction in food intake and adiposity in diet-induced obese rodents consuming palatable high-fat foods.

Topics: Adiposity; Animals; Body Weight; Diet; Dose-Response Relationship, Drug; Eating; Energy Intake; Infusions, Intravenous; Infusions, Parenteral; Male; Obesity; Peptide Fragments; Peptide YY; Rats; Rats, Sprague-Dawley; Weight Gain

Peptide YY (PYY) is a gastrointestinal hormone, localized in enteroendocrine L-cells. Its hydrolyzed form PYY(3-36) is a satiety factor. The aim of this study was to identify if intestinal PYY enteroendocrine cells or content correlate with the diet-induced obese (DIO) or diet-resistant (DR) phenotypes. We also examined intestinal sensitivity to PYY and PYY(3-36) in DIO and DR rats. Animals were maintained on a medium-high fat diet and split into DIO and DR groups based on weight gain. PYY immunoreactive cells were unaltered in DIO intestine and stomach compared to DR rats. PYY content and circulating levels were also unchanged in DIO rats. Intestinal PYY and PYY(3-36) responses were enhanced in fasted rats, and equipotent in both DIO and DR jejunum. We conclude that PYY cell number, tissue content and peripheral sensitivity are maintained in DIO rats. Our data suggests that neither PYY nor PYY(3-36) contribute to the maintenance of either the DIO or DR phenotype, and that peripheral resistance to PYY and PYY(3-36) does not accompany DIO.

Topics: Adipose Tissue; Animals; Body Weight; Diet; Dietary Fats; Eating; Enteroendocrine Cells; Fasting; Feeding Behavior; Male; Obesity; Peptide YY; Rats; Rats, Sprague-Dawley; Weight Gain

Prader-Willi syndrome (PWS) is a contiguous gene syndrome characterized by uncontrollable eating or hyperphagia. Several studies have confirmed that plasma ghrelin levels are markedly elevated in PWS adults and children. The study of anorexigenic hormones is of interest because of their regulation of appetite by negative signals. To study the pattern and response of the anorexigenic hormones such as cholecystokinin (CCK) and peptide YY (PYY) to a meal in PWS, we measured the plasma CCK, PYY, ghrelin and serum insulin levels in PWS patients (n=4) and in controls (n=4) hourly for a day, and analyzed hormone levels and hormonal responses to meals. Repeated measures of ANOVA of hormone levels demonstrated that only insulin levels decreased (p=0.013) and CCK (p=0.005) and ghrelin (p=0.0007) increased in PWS over 24 hr. However, no significant group x time interactions (ghrelin: p=0.89, CCK: p=0.93, PYY: p=0.68 and insulin: p=0.85) were observed; in addition, there were no differences in an assessment of a three-hour area under the curve after breakfast. These results suggest that the response pattern of hormones to meals in PWS patients parallels that of normal controls. In addition, the decrease of insulin levels over 24 hr, in spite of obesity and elevated ghrelin levels, suggests that the baseline insulin level, not the insulin response to meals, may be abnormal in patients with PWS.

Topics: Adolescent; Area Under Curve; Biopsy; Body Mass Index; Body Weight; Child; Cholecystokinin; Ghrelin; Humans; Insulin; Male; Obesity; Peptide Hormones; Peptide YY; Prader-Willi Syndrome; Time Factors

It is well known that the peripheral peptide YY (PYY)-central neuropeptide Y (NPY) Y2 receptor axis plays an important role in promoting negative energy balance regulation. Both the hypothalamus and medulla oblongata express a high level of Y2 receptors; however, the functional role of this receptor in chronic high-fat diet-induced obesity has not been fully examined. Using quantitative autoradiography, this study measured binding densities of total [(125)I]PYY and Y2 receptors in the hypothalamus and medulla of chronic high-fat diet-induced obese (DIO), obese-resistant, and low-fat-fed mice. Plasma PYY was also measured using RIA after 22 wk of dietary intervention. The results revealed that body weight gain was significantly higher in the obese mice, compared with the lean mice. Furthermore, PYY and NPY Y2 receptor binding densities in the medulla of the obese mice were significantly higher, compared with the lean mice, whereas the level of plasma PYY was significantly lower in the DIO mice than the low-fat-fed mice. In conclusion, this study showed that the DIO mice had low plasma PYY, which may have caused a compensatory up-regulation of PYY and Y2 receptor densities in the medulla. A low-level response of PYY-medullary regulation to positive energy balance may have contributed to the development of high-fat diet-induced obesity in DIO mice; conversely, a normal response of this regulatory axis in the obese-resistant mice may have contributed to the maintenance of body weight while on a high-fat diet.

Topics: Adipose Tissue; Animals; Autoradiography; Body Weight; Diet, Fat-Restricted; Dietary Fats; Disease Susceptibility; Energy Intake; Hypothalamus; Medulla Oblongata; Mice; Mice, Inbred C57BL; Obesity; Organ Size; Peptide YY; Receptors, Neuropeptide Y

Selective activation of the neuropeptide Y (NPY)2 receptor to suppress appetite provides a promising approach to obesity management. A selective NPY2 polyethylene glycol-conjugated (PEGylated) peptide agonist is described that consists of a peptide core corresponding to residues 13 to 36 of human peptide YY (PYY) and a nonpeptidic moiety (2-mercaptonicotinic acid) at the peptide N terminus that is derivatized with 20-kDa monomethoxypolyethylene glycol. The PEGylated peptide elicits a dose-dependent reduction in food intake in lean C57BL/6 mice and Wistar rats that persists for 72 and 48 h, respectively. The effect on food intake in lean C57BL/6 mice is blocked by the selective NPY2 antagonist BIIE0246 (N-[(1S)-4-[(aminoiminomethyl)amino]-1-[[[2-(3,5-dioxo-1,2-diphenyl-1,2,4-triazolidin-4-yl)ethyl]amino]carbonyl]butyl]-1-[2-[4-(6,11-dihydro-6-oxo-5H-dibenz[b,e]azepin-11-yl)-1-piperazinyl]-2-oxoethyl]-cyclopentaneacetamide formate). A dose-dependent reduction in body weight in diet-induced obese (DIO) mice is seen following daily dosing for 14 days. The reduction in body weight is sustained following dosing for 40 days, and it is accompanied by an increase in plasma adiponectin. Improvements in glucose disposal and in plasma insulin and glucose levels that are risk factors for type II diabetes are observed following once-daily subcutaneous dosing in DIO mice. The results provide evidence from two animal species that the long-acting selective NPY2 peptide agonist has potential for obesity management.

Topics: Adiponectin; Animals; Appetite Depressants; Arginine; Benzazepines; Body Weight; Dose-Response Relationship, Drug; Eating; Glucose; Humans; Male; Mice; Mice, Inbred C57BL; Peptide Fragments; Peptide YY; Polyethylene Glycols; Rats; Rats, Wistar; Receptors, Neuropeptide Y; Structure-Activity Relationship

Peptide YY (PYY) and pancreatic polypeptide (PPY) are members of the neuropeptide Y peptide family. The neuropeptide Y receptor signaling pathway has been implicated in a number of physiologic processes, including the regulation of energy balance and bone mass. To investigate the contribution of endogenous PYY and PPY to these processes, we generated both Pyy- and Ppy-deficient mice.. Pyy(-/-) and Ppy(-/-) mice and their respective wild-type littermates were studied from 8 weeks to 9 months of age. Food intake, metabolic parameters, and locomotor activity were monitored using indirect calorimetry. Body composition and bone parameters were analyzed using dual energy x-ray absorptiometry, histomorphometry, and vertebral compression testing.. Studies in these mice showed an osteopenic phenotype specific to the Pyy-deficient line, which included a reduction in trabecular bone mass and a functional deficit in bone strength. Furthermore, female Pyy(-/-) mice showed a greater sensitivity to ovariectomy-induced bone loss compared with wild-type littermates. No food intake or metabolic phenotype was apparent in male or female Pyy(-/-) mice on standard chow. However, female Pyy(-/-) mice on a high-fat diet showed a greater propensity to gain body weight and adiposity. No metabolic or osteopenic phenotype was observed in Ppy-deficient mice.. These results indicate that endogenous PYY plays a critical role in regulating bone mass. In comparison, its role in regulating body weight is minor and is confined to situations of high-fat feeding.

Topics: Absorptiometry, Photon; Adiposity; Animals; Body Composition; Body Weight; Bone and Bones; Bone Density; Bone Diseases, Metabolic; Dietary Fats; Disease Models, Animal; Energy Metabolism; Female; Gene Deletion; Male; Mice; Mice, Transgenic; Ovariectomy; Peptide YY; Phenotype; Spine

The responses of the gut hormone peptide YY (PYY) to food were investigated in 20 normal-weight and 20 obese humans in response to six test meals of varying calorie content. Human volunteers had a graded rise in plasma PYY (R2 = 0.96; P < 0.001) during increasing calorific meals, but the obese subjects had a lower endogenous PYY response at each meal size (P < 0.05 at all levels). The ratio of plasma PYY(1-36) to PYY(3-36) was similar in normal-weight and obese subjects. The effect on food intake and satiety of graded doses of exogenous PYY(3-36) was also evaluated in 12 human volunteers. Stepwise increasing doses of exogenous PYY(3-36) in humans caused a graded reduction in food intake (R2 = 0.38; P < 0.001). In high-fat-fed (HF) mice that became obese and low-fat-fed mice that remained normal weight, we measured plasma PYY, tissue PYY, and PYY mRNA levels and assessed the effect of exogenous administered PYY(3-36) on food intake in HF mice. HF mice remained sensitive to the anorectic effects of exogenous ip PYY(3-36). Compared with low-fat-fed fed mice, the HF mice had lower endogenous plasma PYY and higher tissue PYY but similar PYY mRNA levels, suggesting a possible reduction of PYY release. Thus, fasting and postprandial endogenous plasma PYY levels were attenuated in obese humans and rodents. The PYY(3-36) infusion study showed that the degree of plasma PYY reduction in obese subjects were likely associated with decreased satiety and relatively increased food intake. We conclude that obese subjects have a PYY deficiency that would reduce satiety and could thus reinforce their obesity.

Topics: Animals; Body Weight; Eating; Energy Intake; Humans; Mice; Models, Animal; Obesity; Peptide YY; Postprandial Period; Reference Values; Satiety Response

Endogenous peptide YY(3-36) (PYY(3-36)) is associated with postprandial regulation of appetite. We investigated the safety and effectiveness of peripherally administered synthetic human PYY(3-36) for 14 days in New Zealand white rabbits. Weight gain and food consumption were assessed and pharmacokinetics and toxicity characterized.. In all, 24 animals were randomized to one of four intravenous treatment groups - control (0.9% saline) or PYY(3-36) bolus at 4.1, 41.0, or 205 microg/kg/day. Body weight and consumption of fixed food allotment were measured daily. Hematology and serum chemistries were profiled at baseline and Day 15, and pharmacokinetics measured following dose 14. Histopathologic examination of designated tissues and organs in control and PYY(3-36) 205 mug/kg animals was conducted. All animals were subject to clinical and macroscopic observation.. The trend effect of higher dose PYY(3-36) on lower average weight was significant (P = 0.01; Day 14 compared to baseline) and its effect on reduced food consumption was suggested (P = 0.065; number of days < or =75% food eaten, compared with control). Hematology and clinical chemistries were within normal limits pretest and at Day 15. No clinical, macroscopic, histologic, or microscopic changes related to the test article were observed over the course of study.. Lower average weight occurs in rabbits treated once daily with intravenous injection PYY(3-36) (205 microg/kg/day) over 14 days. No clinical or histologic signs of toxicity were observed. Further research is warranted to describe alternate routes of peripheral administration for optimizing weight control.

Topics: Animals; Appetite Depressants; Appetite Regulation; Body Weight; Dose-Response Relationship, Drug; Eating; Female; Infusions, Intravenous; Male; Obesity; Peptide Fragments; Peptide YY; Rabbits; Satiety Response; Weight Gain

Peptide YY (PYY) is an intestinally derived anorexigen that acts via the Y2 receptor, and Y2 receptor deletion in rodents increases bone formation. Anorexia nervosa (AN) is associated with a deliberate reduction in food intake and low bone density, but endocrine modulators of food intake in AN are not known. In addition, known regulators of bone turnover, such as GH, cortisol, and estrogen, explain only a fraction of the variability in bone turnover marker levels.. We hypothesized that PYY may be elevated in AN compared with controls and may contribute to decreased food intake and bone formation.. Fasting PYY was examined in 23 AN girls and 21 healthy adolescents 12-18 yr old. We also examined GH, cortisol, ghrelin, and leptin (overnight frequent sampling) and fasting IGF-I, estradiol, total T3, and bone markers. Macronutrient intake and resting energy expenditure (REE) were measured.. AN girls had higher PYY levels compared with controls (17.8 +/- 10.2 vs. 4.8 +/- 4.3 pg/ml; P < 0.0001). Predictors of log PYY were nutritional markers, including body mass index (r = -0.62; P < 0.0001), fat mass (r = -0.55; P = 0.0003), and REE (r = -0.51; P = 0.0006), and hormones, including GH (r = 0.38; P = 0.004) and T3 (r = -0.59; P = 0.0001). Body mass index, fat mass, REE, GH, and T3 explained 68% of the variability of log PYY. Log PYY predicted percentage of calories from fat (r = -0.56; P = 0.0002) and independently predicted osteocalcin (r = -0.45; P = 0.003), bone-specific alkaline phosphatase (r = -0.46; P = 0.003), N-telopeptide/creatinine (r = -0.55; P = 0.0003), and deoxypyridinoline/creatinine (r = -0.52; P = 0.001) on regression modeling.. Elevated PYY may contribute to reduced intake and decreased bone turnover in AN.

Topics: Adolescent; Anorexia Nervosa; Body Mass Index; Body Weight; Bone and Bones; Estradiol; Female; Ghrelin; Hematocrit; Humans; Hydrocortisone; Peptide Hormones; Peptide YY; Reference Values; Triiodothyronine

In rodents, weight reduction after peptide YY[3-36] (PYY[3-36]) administration may be due largely to decreased food consumption. Effects on other processes affecting energy balance (energy expenditure, fuel partitioning, gut nutrient uptake) remain poorly understood. We examined whether s.c. infusion of 1 mg/(kg x d) PYY[3-36] (for up to 7 d) increased metabolic rate, fat combustion, and/or fecal energy loss in obese mice fed a high-fat diet. PYY[3-36] transiently reduced food intake (e.g., 25-43% lower at d 2 relative to pretreatment baseline) and decreased body weight (e.g., 9-10% reduction at d 2 vs. baseline) in 3 separate studies. Mass-specific metabolic rate in kJ/(kg x h) in PYY[3-36]-treated mice did not differ from controls. The dark cycle respiratory quotient (RQ) was transiently decreased. On d 2, it was 0.747 +/- 0.008 compared with 0.786 +/- 0.004 for controls (P < 0.001); light cycle RQ was reduced throughout the study in PYY[3-36]-treated mice (0.730 +/- 0.006) compared with controls (0.750 +/- 0.009; P < 0.001). Epididymal fat pad weight in PYY[3-36]-treated mice was approximately 50% lower than in controls (P < 0.01). Fat pad lipolysis ex vivo was not stimulated by PYY[3-36]. PYY[3-36] decreased basal gallbladder emptying in nonobese mice. Fecal energy loss was negligible ( approximately 2% of ingested energy) and did not differ between PYY[3-36]-treated mice and controls. Thus, negative energy balance after PYY[3-36] administration in diet-induced obese mice results from reduced food intake with a relative maintenance of mass-specific energy expenditure. Fat loss and reduced RQ highlight the potential for PYY[3-36] to drive increased mobilization of fat stores to help meet energy requirements in this model.

Topics: Adipose Tissue; Animals; Body Weight; Calorimetry; Dietary Fats; Energy Metabolism; Male; Mice; Mice, Inbred C57BL; Obesity; Peptide Fragments; Peptide YY

Obese people exhibit reduced circulating peptide YY (PYY) levels, but it is unclear whether this is a consequence or cause of obesity. We therefore investigated the effect of Pyy ablation on energy homeostasis.. Body composition, i.p. glucose tolerance, food intake and hypothalamic neuropeptide expression were determined in Pyy knock-out and wild-type mice on a normal or high-fat diet.. Pyy knock-out significantly increased bodyweight and increased fat mass by 50% in aged females on a normal diet. Male chow-fed Pyy (-/-) mice were resistant to obesity but became significantly fatter and glucose-intolerant compared with wild-types when fed a high-fat diet. Pyy knock-out animals exhibited significantly elevated fasting or glucose-stimulated serum insulin concentrations vs wild-types, with no increase in basal or fasting-induced food intake. Pyy knock-out decreased or had no effect on neuropeptide Y expression in the arcuate nucleus of the hypothalamus, and significantly increased proopiomelanocortin expression in this region. Male but not female knock-outs exhibited significantly increased growth hormone-releasing hormone expression in the ventromedial hypothalamus and significantly elevated serum IGF-I and testosterone levels. This sex difference in activation of the hypothalamo-pituitary somatotrophic axis by Pyy ablation may contribute to the resistance of chow-fed male knock-outs to late-onset obesity.. PYY signalling is important in the regulation of energy balance and glucose homeostasis, possibly via regulation of insulin release. Therefore reduced PYY levels may predispose to the development of obesity, particularly with ageing or under conditions of high-fat feeding.

Topics: Adipose Tissue; Animals; Body Weight; Chromosomes, Artificial, Bacterial; Cloning, Molecular; DNA Primers; Energy Intake; Female; Glucose Tolerance Test; Hyperinsulinism; Male; Mice; Mice, Knockout; Obesity; Organ Size; Peptide YY; Polymerase Chain Reaction; Restriction Mapping; Sex Characteristics

The gut hormone peptide YY (PYY) was recently proposed to comprise an endogenous satiety factor. We have studied acute anorectic functions of PYY(3-36) in mice and rats, as well as metabolic effects of chronic PYY(3-36) administration to diet-induced obese (DIO) mice and rats. A single intraperitoneal injection of PYY(3-36) inhibited food intake in mice, but not in rats. We next investigated the effects of increasing doses (100, 300, and 1,000 microg.kg-1.day-1) of PYY(3-36) administered subcutaneously via osmotic minipumps on food intake and body weight in DIO C57BL/6J mice. Whereas only the highest dose (1,000 microg.kg-1.day-1) of PYY(3-36) significantly reduced food intake over the first 3 days, body weight gain was dose dependently reduced, and on day 28 the group treated with 1,000 microg.kg-1.day-1 PYY(3-36) weighed approximately 10% less than the vehicle-treated group. Mesenteric, epididymal, retroperitoneal, and inguinal fat pad weight was dose dependently reduced. Subcutaneous administration of PYY(3-36) (250 and 1,000 microg.kg-1.day-1) for 28 days reduced body weight and improved glycemic control in glucose-intolerant DIO rats. Neither 250 nor 1,000 microg/kg PYY(3-36) elicited a conditioned taste aversion in male rats.

Topics: Animals; Blood Glucose; Body Weight; Disease Models, Animal; Drug Administration Routes; Eating; Feeding Behavior; Insulin; Male; Mice; Mice, Inbred C57BL; Motor Activity; Obesity; Peptide Fragments; Peptide YY; Rats; Rats, Sprague-Dawley; Rats, Wistar; Rodentia; Taste

Dietary protein enhances satiety and promotes weight loss, but the mechanisms by which appetite is affected remain unclear. We investigated the role of gut hormones, key regulators of ingestive behavior, in mediating the satiating effects of different macronutrients. In normal-weight and obese human subjects, high-protein intake induced the greatest release of the anorectic hormone peptide YY (PYY) and the most pronounced satiety. Long-term augmentation of dietary protein in mice increased plasma PYY levels, decreased food intake, and reduced adiposity. To directly determine the role of PYY in mediating the satiating effects of protein, we generated Pyy null mice, which were selectively resistant to the satiating and weight-reducing effects of protein and developed marked obesity that was reversed by exogenous PYY treatment. Our findings suggest that modulating the release of endogenous satiety factors, such as PYY, through alteration of specific diet constituents could provide a rational therapy for obesity.

Topics: Animals; Appetite Regulation; Body Weight; Dietary Proteins; Disease Models, Animal; Enteroendocrine Cells; Feeding Behavior; Food, Formulated; Gastrointestinal Tract; Hormones; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Obesity; Peptide YY; Satiety Response; Up-Regulation

To explore the potential role of the endogenous peptide YY (PYY) in the long-term regulation of body weight and energy homeostasis.. Fasting and postprandial plasma PYY concentrations were measured after an overnight fast and 30 to 180 minutes after a standardized meal in 29 (21 men/8 women) non-diabetic subjects, 16 of whom had a follow-up visit 10.8 +/- 1.4 months later. Ratings of hunger and satiety were collected using visual analog scales. Resting metabolic rate (RMR) (15-hour RMR) and respiratory quotient (RQ) were assessed using a respiratory chamber.. Fasting PYY concentrations were negatively correlated with various markers of adiposity and negatively associated with 15-hour RMR (r = -0.46, p = 0.01). Postprandial changes in PYY (area under the curve) were positively associated with postprandial changes in ratings of satiety (r = 0.47, p = 0.01). The maximal PYY concentrations achieved after the meal (peak PYY) were negatively associated with 24-hour RQ (r = -0.41, p = 0.03). Prospectively, the peak PYY concentrations were negatively associated with changes in body weight (r = -0.58, p = 0.01).. Our data indicate that the endogenous PYY may be involved in the long-term regulation of body weight. It seems that this long-term effect was not exclusively driven by the modulation of food intake but also by the control of energy expenditure and lipid metabolism.

Topics: Adolescent; Adult; Area Under Curve; Basal Metabolism; Blood Glucose; Body Weight; Energy Metabolism; Fasting; Female; Glucose Tolerance Test; Humans; Hunger; Insulin; Lipid Metabolism; Male; Middle Aged; Obesity; Oxygen Consumption; Peptide YY; Postprandial Period; Satiety Response

Topics: Animals; Appetite Regulation; Body Weight; Gastrointestinal Tract; Humans; Peptide Fragments; Peptide YY

Adiponectin (Acrp30) and peptide YY (PYY) are weight-regulatory hormones participating in the control of energy homeostasis. This study investigated the effects of long-term wintertime fasting on plasma Acrp30 and PYY levels in the carnivorous blue fox, a farm-bred variant of the arctic fox (Alopex lagopus). Plasma Acrp30 and PYY concentrations were determined with radioimmunoassays during a 22-day period of fasting, which led to a 20.3% reduction in body mass of the animals (n=32). Sixteen fed blue foxes served as the control group. Acrp30 and PYY were present in blue fox plasma at similar or lower levels as reported previously for other mammals. Fasting had no acute effects on Acrp30 or PYY concentrations of the blue foxes. However, the Acrp30 levels of the fasted blue foxes were 24%-48% higher than in the fed animals between days 8-22 of fasting. Fasted blue foxes also had 6.2-fold higher plasma PYY concentrations after 15 days of fasting. Acrp30 and PYY seem to play roles in the body weight-regulation of the blue fox during long-term fasting, but their specific functions and physiological significance remain to be determined.

Topics: Adiponectin; Animals; Animals, Domestic; Body Weight; Fasting; Female; Foxes; Intercellular Signaling Peptides and Proteins; Male; Peptide YY

PYY (3-36) is postulated to act as a satiety factor in the gut-hypothalamic pathway to inhibit food intake and body weight gain in humans and rodent models. We determined the effect of 14-day continuous intravenous infusion of PYY (3-36) (175 microg/kg/day) on food intake and body weight gain in colectomized male Wistar rats. Colectomy caused an increase in plasma PYY levels at 7 days which was reduced at 14 days but still significantly elevated compared to basal preoperative values. Animals treated with continuous PYY (3-36) infusion had significantly elevated PYY levels compared to the control group throughout the whole experiment, but showed a similar pattern of food intake and body weight gain. In conclusion, although continuous intravenous infusion is the most physiologically relevant method to mimic high postprandial PYY levels, we did not observe any significant effect on food intake and body weight gain in non-food deprived colectomized animals. This suggests that PYY has, if at all, only a minor role in food intake in rats.

Topics: Animals; Body Weight; Colectomy; Eating; Humans; Infusion Pumps, Implantable; Male; Peptide YY; Rats; Rats, Wistar

We determined whether Roux-en-Y gastric bypass (RYGB)-induced protracted weight loss is associated with an increase in anorectic peptide YY (PYY) and decreased gastrointestinal (GI) motility.. RYGB and control sham-operated GI intact obese (SO Obese) and sham-operated GI intact pair-fed (PF) rats were studied. Postoperatively, body weight (BW) and food intake were measured for 90 days. Rats were killed to measure PYY, ghrelin, cholecystokinin (CCK), and glucagonlike peptide-1 (GLP-1). Ninety-day food intake trends were examined by quadratic trend analysis. On the basis of a 28-day weight loss rate, PYY also was measured at 14 and 28 days. Peak 28-day PYY results corresponded with peak BW loss rate; thus, gastric emptying (GE) and intestinal transit time were measured. Data were analyzed by analysis of variance and Tukey's pairwise multiple comparison.. At 90 days, BW in SO Obese versus PF versus RYGB rats was 801 +/- 15 g versus 661 +/- 24 g versus 538 +/- 32 g respectively (P < .05). Concentrations of plasma PYY were increased, while plasma ghrelin was decreased in RYGB versus SO Obese and PF (P < .05). CCK and GLP-1 were unchanged. In RYGB versus controls, PYY was increased at 14 and 28 days but was most elevated at 28 days. In RYGB versus controls, GE was delayed (P < .05) and intestinal transit time was longer (P < .05).. After RYGB, an increase in PYY and a decrease in ghrelin occurred, probably explaining the decrease in food intake, the slower GE and transit time, which contributed to weight loss. Longitudinal studies can be performed with the use of our RYGB model, providing insight into weight loss mechanisms by generating long-term follow-up data currently not available in human studies.

Topics: Anastomosis, Roux-en-Y; Animals; Body Weight; Eating; Gastric Bypass; Gastric Emptying; Gastrointestinal Motility; Ghrelin; Male; Obesity; Peptide Hormones; Peptide YY; Postoperative Period; Rats; Rats, Sprague-Dawley

Peptide YY (PYY) and ghrelin are gastrointestinal tract-derived hormones that play roles in the regulation of food intake and energy balance. Negative energy balance often occurs in hospitalized preterm infants.. To measure serum concentrations of PYY in preterm and full-term infants and to investigate their correlations with anthropometric characteristics, food intake, and serum ghrelin concentrations, we measured serum PYY and ghrelin concentrations by RIA in 62 healthy preterm infants [mean (SD) gestational age, 32.0 (2.1) weeks; postnatal age, 40.9 (14.8) days] and 15 healthy full-term infants of comparable postnatal age. All of the infants were formula-fed every 3 h.. PYY concentrations were significantly higher in preterm [1126.2 (215.4) ng/L] than in full-term infants [825.3 (234.4) ng/L; P < 0.001]. In the entire study population, serum PYY concentrations correlated negatively with gestational age and anthropometric measurements (birth weight, body weight, body length, body mass index, and head circumference) and positively with serum ghrelin concentrations, whereas there was no significant correlation between PYY concentration and caloric intake or weight gain. Multiple regression analysis, after correction for prematurity, revealed that serum PYY concentrations correlated independently with serum ghrelin concentrations and infant body weight or body mass index.. Circulating concentrations of PYY may increase in preterm infants to compensate for the negative body-weight balance. The physiologic mechanisms behind the correlation between PYY and ghrelin remain to be elucidated.

Topics: Anthropometry; Body Weight; Gestational Age; Ghrelin; Humans; Infant, Newborn; Infant, Premature; Peptide Hormones; Peptide YY; Regression Analysis

Inactivating mutations of the pro-opiomelanocortin (POMC) gene in both mice and humans leads to hyperphagia and obesity. To further examine the mechanisms whereby POMC-deficiency leads to disordered energy homeostasis, we have generated mice lacking all POMC-derived peptides. Consistent with a previously reported model, Pomc(-/-) mice were obese and hyperphagic. They also showed reduced resting oxygen consumption associated with lowered serum levels of thyroxine. Hypothalami from Pomc(-/-) mice showed markedly increased expression of melanin-concentrating hormone mRNA in the lateral hypothalamus, but expression of neuropeptide Y mRNA in the arcuate nucleus was not altered. Provision of a 45% fat diet increased energy intake and body weight in both Pomc(-/-) and Pomc(+/-) mice. The effects of leptin on food intake and body weight were blunted in obese Pomc(-/-) mice whereas nonobese Pomc(-/-) mice were sensitive to leptin. Surprisingly, we found that Pomc(-/-) mice maintained their acute anorectic response to peptide-YY(3-36) (PYY(3-36)). However, 7 days of PYY(3-36) administration had no effect on cumulative food intake or body weight in wild-type or Pomc(-/-) mice. Thus, POMC peptides seem to be necessary for the normal response of energy balance to high-fat feeding, but not for the acute anorectic effect of PYY(3-36) or full effects of leptin on feeding. The finding that the loss of only one copy of the Pomc gene is sufficient to render mice susceptible to the effects of high fat feeding emphasizes the potential importance of this locus as a site for gene-environment interactions predisposing to obesity.

Topics: Animals; Appetite Depressants; Base Sequence; Body Weight; Dietary Fats; DNA Primers; Energy Intake; Hypothalamic Hormones; Hypothalamus; Kinetics; Leptin; Melanins; Mice; Mice, Knockout; Mutagenesis, Site-Directed; Neuropeptide Y; Obesity; Peptide Fragments; Peptide YY; Phenotype; Pituitary Hormones; Polymerase Chain Reaction; Pro-Opiomelanocortin; Transcription, Genetic

Peptide YY (PYY) is a 36 amino-acid peptide secreted from ileal L cells following meals. The cleaved subpeptide PYY[3-36] is biologically active and may constitute the majority of circulating PYY-like immunoreactivity. The peptide family that includes PYY, pancreatic peptide and neuropeptide Y is noted for its orexigenic effect following intracerebroventricular administration.. To investigate the effects of peripheral (intraperitoneal and chronic subcutaneous) infusions of PYY[3-36] on food intake, body weight and glycemic indices.. Food intake was measured in normal mice and in several rodent models of obesity and type II diabetes. In marked contrast to the reported central orexigenic effects, in the present study, PYY[3-36] acutely inhibited food intake by up to 45%, with an ED(50) of 12.5 microg/kg in fasted female NIH/Swiss mice. A 4-week infusion reduced weight gain in female ob/ob mice, without affecting the cumulative food intake. In diet-induced obese male mice, PYY[3-36] infusion reduced cumulative food intake, weight gain and epididymal fat weight (as a fraction of carcass) with similar ED(50)'s (466, 297 and 201 microg/kg/day, respectively) and prevented a diet-induced increase in HbA1c. Infusion at 100 microg/kg/day for 8 weeks in male fa/fa rats reduced the weight gain (288+/-11 vs 326+/-12 g in saline-infused controls; P<0.05), similar to effects in a pair-fed group. In female ob/ob and db/db mice, there was no acute effect of PYY[3-36] on plasma glucose concentrations. In male diabetic fatty Zucker rats, PYY[3-36] infused for 4 weeks reduced HbA1c and fructosamine (ED(50)'s 30 and 44 microg/kg/day).. Peripheral PYY[3-36] administration reduced the food intake, body weight gain and glycemic indices in diverse rodent models of metabolic disease of both sexes. These findings justify further exploration of the potential physiologic and therapeutic roles of PYY[3-36].

Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Implants; Eating; Energy Intake; Female; Infusions, Intravenous; Injections, Intraperitoneal; Male; Mice; Mice, Mutant Strains; Models, Animal; Obesity; Peptide Fragments; Peptide YY; Rats; Rats, Inbred Strains; Rats, Zucker

Batterham et al. report that the gut peptide hormone PYY3-36 decreases food intake and body-weight gain in rodents, a discovery that has been heralded as potentially offering a new therapy for obesity. However, we have been unable to replicate their results. Although the reasons for this discrepancy remain undetermined, an effective anti-obesity drug ultimately must produce its effects across a range of situations. The fact that the findings of Batterham et al. cannot easily be replicated calls into question the potential value of an anti-obesity approach that is based on administration of PYY3-36.

Topics: Animals; Animals, Inbred Strains; Appetite; Appetite Depressants; Appetite Regulation; Behavior, Animal; Body Weight; Environment; Feeding Behavior; Humans; Meta-Analysis as Topic; Mice; Obesity; Peptide Fragments; Peptide YY; Rats; Reproducibility of Results; Stress, Physiological

The raccoon dog (Nyctereutes procyonoides) is an omnivorous canid utilizing the passive wintering strategy in the boreal climate. Farmed raccoon dogs (n=12) were randomly assigned into two study groups on 26 November 2003. Between 3 December 2003 and 27 January 2004, half of the animals were fasted for 8 weeks and plasma weight-regulatory hormone concentrations determined on 26 November and 30 December 2003 and on 27 January 2004. The plasma peptide YY, ghrelin, and growth hormone (GH) concentrations increased due to food deprivation, while the T4 and Acrp30 concentrations decreased. Furthermore, the plasma GH concentrations were higher in the fasted raccoon dogs than in the fed animals, which had higher plasma insulin, glucagon, and T4 concentrations. However, fasting had no effect on the plasma leptin concentrations. The results confirm previous findings with unchanged leptin levels in fasting carnivores. Increased GH levels probably contribute to increased lipolysis and mobilization of fat stores. Ghrelin can also enhance lipolysis by increasing the GH levels. The decreased levels of T4 may reduce the metabolic rate. The plasma dopamine concentrations decreased due to fasting unlike observed previously in rats. Together with the unaffected adrenaline, noradrenaline, and cortisol concentrations, this suggests that food deprivation in winter does not cause stress to the raccoon dog but is an integral part of its natural life history.

Topics: Adaptation, Physiological; Adiponectin; Adipose Tissue; Analysis of Variance; Animals; Body Weight; Catecholamines; Dopamine; Fasting; Female; Ghrelin; Glucagon; Growth Hormone; Hydrocortisone; Insulin; Intercellular Signaling Peptides and Proteins; Leptin; Peptide Hormones; Peptide YY; Raccoon Dogs; Random Allocation; Seasons; Thyroxine

Topics: Animals; Appetite; Appetite Depressants; Body Weight; Dose-Response Relationship, Drug; Gastric Emptying; Humans; Macaca mulatta; Peptide Fragments; Peptide YY; Rats

Topics: Agouti-Related Protein; alpha-MSH; Animals; Anti-Obesity Agents; Appetite; Arcuate Nucleus of Hypothalamus; Body Weight; Brain; Caloric Restriction; Fatty Acids; Ghrelin; Humans; Insulin; Intercellular Signaling Peptides and Proteins; Leptin; Longevity; Mice; Neurons; Neuropeptide Y; Obesity; Peptide Hormones; Peptide YY; Pro-Opiomelanocortin; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Protein Tyrosine Phosphatases; Proteins; Receptor, Insulin; Receptors, Pituitary Hormone; Stearoyl-CoA Desaturase

Intestinal morphology and expression of brush border enzymes can be dramatically altered by nutrient composition and position along the longitudinal gut axis. In contrast, endocrine gene expression appears to be relatively "imprinted" and is not significantly altered by positional changes. The purpose of our study was to assess the effects of transposing the ileum into the colonic position on intestinal morphology, gene expression, and enzyme activity. For this study, male Sprague-Dawley rats underwent either transposition of an approximately 8-cm segment of distal ileum into the colonic position or sham operation. Rats were sacrificed 2 months after operation and transposed or sham ileum was assessed. We found that transposition of the ileum to the colonic position resulted in no change in the ileal mucosal architecture. Furthermore, no change in the expression of the endocrine genes neurotensin and PYY or the apoptotic genes was detected. Although sucrase-isomaltase activity was decreased in the transposed ileum, this decrease did not achieve statistical significance. These results demonstrate that the ileum can be successfully interposed into the colonic position. In this location, the ileum functions normally without changes in the villus morphology or gene expression pattern despite the change in position and composition of the luminal content.

Topics: Animals; Apoptosis; Body Weight; Colon; Gene Expression; Genomic Imprinting; Ileum; Intestinal Mucosa; Male; Neurotensin; Peptide YY; Rats; Rats, Sprague-Dawley; Sucrase-Isomaltase Complex

Pancreatic polypeptide (PP) belongs to a family of peptides including neuropeptide Y and peptide YY. We examined the role of PP in the regulation of body weight as well as the therapeutic potential of PP.. We measured food intake, gastric emptying, oxygen consumption, and gene expression of hypothalamic neuropeptides, gastric ghrelin, and adipocytokines in mice after administering PP intraperitoneally. Peptide gene expression was also examined in PP-overexpressing mice. Vagal and sympathetic nerve activities were recorded after intravenous administration in rats. Effects of repeated administrations of PP on energy balance and on glucose and lipid metabolism were examined in both ob/ob obese mice and fatty liver Shionogi (FLS)-ob/ob obese mice.. Peripherally administered PP induced negative energy balance by decreasing food intake and gastric emptying while increasing energy expenditure. The mechanism involved modification of expression of feeding-regulatory peptides (decrease in orexigenic neuropeptide Y, orexin, and ghrelin along with an increase in anorexigenic urocortin) and activity of the vagovagal or vagosympathetic reflex arc. PP reduced leptin in white adipose tissue and corticotropin-releasing factor gene expression. The expression of gastric ghrelin and hypothalamic orexin was decreased in PP-overexpressing mice. Repeated administrations of PP decreased body weight gain and ameliorated insulin resistance and hyperlipidemia in both ob/ob obese mice and FLS-ob/ob obese mice. Liver enzyme abnormalities in FLS-ob/ob obese mice were also ameliorated by PP.. These observations indicate that PP may influence food intake, energy metabolism, and the expression of hypothalamic peptides and gastric ghrelin.

Topics: Animals; Body Weight; Carrier Proteins; Disease Models, Animal; Eating; Energy Metabolism; Gastric Emptying; Gene Expression; Ghrelin; Hypothalamus; Injections, Intraperitoneal; Intracellular Signaling Peptides and Proteins; Male; Mice; Neuropeptide Y; Neuropeptides; Obesity; Orexins; Oxygen Consumption; Pancreatic Polypeptide; Peptide Hormones; Peptide YY

Obesity is a growing epidemic, causally associated with a number of serious medical conditions, including diabetes mellitus, coronary heart disease, and several cancers. The gut hormones ghrelin and peptide YY are secreted from the gut in response to changes to nutritional status. While food intake is stimulated by ghrelin, it is inhibited by peptide YY. The discovery, anatomy, and physiology of ghrelin and peptide YY are discussed, focusing on the adaptive changes in diseases such as obesity and anorexia nervosa. Ghrelin and PYY are important therapeutic targets in the quest to find an effective antiobesity treatment.

Topics: Appetite; Body Weight; Eating; Fasting; Gastric Bypass; Ghrelin; Humans; Hypothalamus; Obesity, Morbid; Peptide Hormones; Peptide YY

Topics: Animals; Appetite; Arcuate Nucleus of Hypothalamus; Body Weight; Energy Intake; Feeding Behavior; Humans; Mice; Neurons; Peptide Fragments; Peptide YY; Receptors, Neuropeptide Y; Signal Transduction

Food intake is regulated by the hypothalamus, including the melanocortin and neuropeptide Y (NPY) systems in the arcuate nucleus. The NPY Y2 receptor (Y2R), a putative inhibitory presynaptic receptor, is highly expressed on NPY neurons in the arcuate nucleus, which is accessible to peripheral hormones. Peptide YY(3-36) (PYY(3-36)), a Y2R agonist, is released from the gastrointestinal tract postprandially in proportion to the calorie content of a meal. Here we show that peripheral injection of PYY(3-36) in rats inhibits food intake and reduces weight gain. PYY(3-36) also inhibits food intake in mice but not in Y2r-null mice, which suggests that the anorectic effect requires the Y2R. Peripheral administration of PYY(3-36) increases c-Fos immunoreactivity in the arcuate nucleus and decreases hypothalamic Npy messenger RNA. Intra-arcuate injection of PYY(3-36) inhibits food intake. PYY(3-36) also inhibits electrical activity of NPY nerve terminals, thus activating adjacent pro-opiomelanocortin (POMC) neurons. In humans, infusion of normal postprandial concentrations of PYY(3-36) significantly decreases appetite and reduces food intake by 33% over 24 h. Thus, postprandial elevation of PYY(3-36) may act through the arcuate nucleus Y2R to inhibit feeding in a gut-hypothalamic pathway.

Topics: Action Potentials; Animals; Appetite; Arcuate Nucleus of Hypothalamus; Body Weight; Electrophysiology; Energy Intake; Feeding Behavior; Gene Deletion; Humans; Injections, Intraperitoneal; Injections, Intraventricular; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurons; Peptide Fragments; Peptide YY; Pro-Opiomelanocortin; Proto-Oncogene Proteins c-fos; Rats; Rats, Wistar; Receptors, Neuropeptide Y; Signal Transduction

The effects of in ovo peptide YY (PYY) or epidermal growth factor (EGF) administration on chick growth, yolk absorption and yolk stalk function in posthatch (0-5 days) meat-type or broiler chicks were determined. At Day 18 of incubation, treated eggs were injected into the air cell with 100 microl of either PYY (Trial 1) or EGF (Trial 2) at a dosage of 600 microg/kg egg weight. Saline-treated control eggs were injected similarly with 0.9% saline. At hatch, 200 microl of (51)Cr-labeled microspheres were injected into chick yolk sacs. Epidermal growth factor increased ileal wet weight adjusted for body weight as well as ileal serosal dry matter. Body weight, feed consumption and excreta weight per bird, and relative weights of the yolk sac, intestine and liver were significantly affected by age of the chick in both trials. Relative radioactivity of the yolk sac, yolk stalk, blood, liver, and kidneys were affected by bird age in Trial 2; however, there were no significant effects due to PYY or EGF treatments on relative radioactivity of the tissues and organs examined. These data suggest that PYY and EGF had no effect on yolk absorption or yolk stalk function through 5 days in the posthatch chick.

Topics: Animals; Body Weight; Chickens; Egg Yolk; Epidermal Growth Factor; Intestines; Liver; Organ Size; Ovum; Peptide YY; Time Factors

Keratinocyte growth factor (KGF) is a potent mitogen and may be of value for the treatment of conditions such as short bowel syndrome and chemotherapy-induced mucositis. However the most efficacious route and method of administration is unclear.. Rats maintained by total parenteral nutrition (TPN) were given KGF (1 mg/kg/rat/day, i.v.) infused continuously or as a once-daily injection. The same dose was also given s.c. to chow-fed rats. Changes in gut growth were assessed by measurement of wet weight, proliferation (vincristine induced metaphase arrest) and crypt branching index. Changes in gut hormone profile were also determined to examine if any trophic effects were mediated via this mechanism.. KGF caused a 70-100% increase in wet weight of the stomach, small and large intestine of TPN-fed rats (P < 0.01) with no significant differences seen between the two methods of administration. The increase in metaphase counts was greatest in the stomach (about seven-fold P < 0.01), but was less pronounced in the distal small intestine and colon (about 50% increase). The trophic effect of KGF was much less prominent in orally-fed rats. Crypt branching index was significantly reduced by KGF in the proximal small intestine of TPN, but not orally-fed rats. Plasma gastrin, PYY, total glucagon, enteroglucagon and GLP-1 all increased by two-three-fold (all P < 0.01) in response to KGF whereas insulin levels fell by about 25% in the TPN group.. The mitogenic action of KGF occurred predominantly in the stomach and proximal small intestine. Its efficacy was less pronounced in orally-fed animals, suggesting KGF may be of greatest benefit in conditions associated with lowered intestinal proliferation. Clinical trials of KGF can probably use single daily i.v. injections without reduction in efficacy.

Topics: Animals; Body Weight; Fibroblast Growth Factor 10; Fibroblast Growth Factor 7; Fibroblast Growth Factors; Gastrins; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Growth Substances; Intestinal Mucosa; Male; Metaphase; Organ Size; Peptide Fragments; Peptide YY; Protein Precursors; Rats; Rats, Wistar

The effects of in ovo Peptide YY (PYY) administration on growth and feed conversion ratios in a commercial broiler line were investigated. Six hundred Ross male x Cobb female eggs were administered either 0.9% saline (control) or 600 microg/kg egg weight PYY in ovo at Day 18 of incubation. On day of hatching, 210 birds from each treatment group were randomly placed by sex into pens. Body weights at placement were not different between treatment groups. Average chick body weight and adjusted pen feed conversion ratios were improved by PYY in ovo treatment at 7 d posthatch (165.7 vs. 170.2 g, P<0.02; and 1.55 vs. 1.49, P<0.04, respectively). No significant differences between treatments were noted for these parameters at 21 or 42 d of age. These results suggest that in ovo treatment of broiler chicken eggs with gastrointestinal hormones that increase intestinal nutrient absorption, such as PYY, may enhance chick performance.

Topics: Animals; Body Weight; Chickens; Eggs; Energy Metabolism; Female; Growth; Male; Nutritional Status; Peptide YY

Neuropeptide Y (NPY), a 36-amino-acid neuromodulator abundantly expressed in the brain, has been implicated in the regulation of food intake and body weight. Pharmacological data suggest that NPY's stimulatory effect on appetite is transduced by the G-protein-coupled NPY Y5 receptor (Y5R). We have inactivated the Y5R gene in mice and report that younger Y5R-null mice feed and grow normally; however, they develop mild late-onset obesity characterized by increased body weight, food intake and adiposity. Fasting-induced refeeding is unchanged in younger Y5R-null mice and they exhibit normal sensitivity to leptin. Their response to intracerebroventricular (i.c.v.) administration of NPY and related peptides is either reduced or absent. NPY deficiency attenuates the obesity syndrome of mice deficient for leptin (ob/ob), but these effects are not mediated by NPY signaling through the Y5R because Y5R-null ob/ob mice are equally obese. These results demonstrate that the Y5R contributes to feeding induced by centrally administered NPY and its analogs, but is not a critical physiological feeding receptor in mice.

Topics: Animals; Body Weight; Dose-Response Relationship, Drug; Feeding Behavior; Female; Genotype; Humans; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Mutant Strains; Molecular Sequence Data; Mutagenesis, Site-Directed; Mutation; Neuropeptide Y; Obesity; Pancreatic Polypeptide; Peptide YY; Peptides, Cyclic; Phenotype; Proteins; Receptors, Neuropeptide Y; RNA, Messenger; Time Factors

The effects of neuropeptide Y (NPY), peptide YY (PYY), [Leu31, Pro34]NPY, and NPY (13-36) on adipocyte lipolysis have been studied in subcutaneous (inguinal) and visceral (parametrial) rat adipose tissues. A 48-h fasting period and chemical sympathectomy were used to evaluate the regulation of Y1 and Y2 pathways in rat adipocytes. NPY, PYY, and [Leu31, Pro34]NPY significantly inhibited fat cell lipolysis by about 25% in both tissues (p < or = 0.05). This inhibition was achieved mainly through the Y1 pathway. No significant response to NPY (13-36) was observed, suggesting a lack of involvement of the Y2 pathway in the antilipolytic effect of NPY and PYY. The 48-h fasting period led to the loss of the Y1 inhibitory effect previously observed in control rats. On the other hand, the chemical sympathectomy induced a 35% increase of fat cell lipolysis (p < or = 0.05). The latter involved the Y2 pathway as stimulated by NPY (13-36), and was observed in the parametrial tissue exclusively. These results suggest that: a) rat Y receptors reported to exhibit Gi responses can also express Gs-like responses, and b) visceral and subcutaneous adipose tissues exhibit specific regulation of fat cell lipolysis.

Topics: Adipocytes; Animals; Appetite Stimulants; Body Weight; Cell Size; Eating; Fasting; Female; Lipolysis; Neuropeptide Y; Oxidopamine; Peptide Fragments; Peptide YY; Rats; Rats, Wistar; Receptors, Neuropeptide Y; Sympathectomy, Chemical; Sympatholytics

Maintaining rats on TPN for 7 days was associated with a 50% reduction in gut mass and protein content. Co-infusing PYY with total parenteral nutrition (TPN) resulted in significant savings in jejunal wet mass and elevated protein content of jejunum, ileum and colon as compared with rats maintained on TPN alone. No significant effects of PYY on plasma amino acid profile were noted. Although minor alterations in mucosal polyamines were observed in rats maintained on TPN, co-infusion of PYY had no significant effect on gut polyamine concentrations. These results suggest that PYY has trophic effects upon the gut during otherwise catabolic conditions. Therefore, co-infusion of PYY with TPN may suggest methods whereby loss of intestinal mucosa and atrophy-associated complications of TPN may be modulated.

Topics: Animals; Body Weight; Intestinal Mucosa; Male; Parenteral Nutrition, Total; Peptide YY; Peptides; Proteins; Rats; Rats, Sprague-Dawley

Peptide YY (PYY), a 36 amino acid enteric hormone, is known to decrease pancreatic exocrine and endocrine function. Previous studies with BIM-43004-1, a modified PYY(22-36) Y2 receptor agonist, have revealed diminished mitochondrial activity in pretreated pancreatic cancer cells in vitro. We investigated the effects of both PYY and BIM-43004-1 on pancreatic cancer growth in vivo.. The 100,000 to 150,000 human pancreatic cancer cells, Mia PaCa-2, were orthotopically transplanted into 48 male athymic mice. After 1 week animals were treated with either PYY or BIM-43004-1 at 200 pmol/kg/hr via miniosmotic pumps for 2, 3, or 4 weeks. Paired controls received saline solution. At death tumor size and mass were measured. Receptor binding studies and intracellular cyclic adenosine monophosphate (cAMP) levels were measured in vitro.. All mice had significant human cancer growth within the pancreas by histologic sections at 2, 3, and 4 weeks. Tumor mass was decreased by 60.5% in BIM-43004-1 treated mice and 27.1% in PYY treated mice. Receptor binding studies revealed binding of [125I]-BIM-43004-1 and displacement of ligand on competitive addition of nonradioactive BIM-43004-1. K dissociation constant of 4.5 nmol and 27,000 receptors per cell were quantitated by receptor binding studies. In BIM-43004-1 treated pancreatic cells a 52.5% decrease in intracellular cAMP levels was noted, whereas a 15.3% decrease was seen in PYY treated cells.. BIM-43004-1, a novel Y2 synthetic agonist, specifically binds to human pancreatic cancer cells, decreases intracellular cAMP levels, and suppresses tumor growth in vivo. Adjuvant hormonal treatment with this Y2 receptor analog may be beneficial in the treatment of patients with pancreatic adenocarcinoma.

Topics: Animals; Body Weight; Cell Division; Cyclic AMP; Gastrointestinal Hormones; Humans; Intracellular Membranes; Male; Mice; Mice, Nude; Pancreatic Neoplasms; Peptide Fragments; Peptide YY; Peptides; Receptors, Gastrointestinal Hormone; Tumor Cells, Cultured

Short-chain fatty acids (SCFAs) are trophic to small intestinal and colonic mucosa. This study determined whether SCFAs infused into the cecum out of continuity stimulated jejunal and colonic cellularity and whether these effects were mediated by the autonomic nervous system and/or enterotrophic hormones.. To eliminate direct trophic effects of SCFAs in contact with mucosa, 60 rats underwent cecal isolation with placement of an infusion catheter into the proximal cecum, formation of distal cecocutaneous stoma, and restoration of intestinal continuity with ileocolonic anastomosis. Rats underwent cecal denervation or remained normally innervated and received 1 of 3 infusions for 10 days: SCFAs, saline, or no infusion. Twenty-four additional rats were assigned to the same groups but underwent infusion into the proximal colon (in circuit).. Cecal infusion of SCFAs into innervated rats increased (P < 0.05) jejunal DNA, villous height, surface area, crypt depth, and gastrin without increasing colonic variables. In denervated rats, SCFAs did not significantly affect these variables. However, direct intracolonic infusions of SCFAs increased (P < 0.05) colonic mucosal DNA and crypt depth.. Jejunotrophic effects of cecally infused SCFAs are mediated afferently by the autonomic nervous system and are associated with increased jejunal gastrin. SCFAs have local trophic effects on the colon.

Topics: Animals; Body Weight; Cecum; Colon; Denervation; DNA; Fatty Acids, Volatile; Gastrins; Jejunum; Male; Peptide YY; Peptides; Proteins; Rats; Rats, Sprague-Dawley

The related central nervous system peptides neuropeptide Y and peptide YY have been found to be among the most potent endogenous stimulants of feeding behavior. We measured these neuropeptides in cerebrospinal fluid to determine whether they contributed to the pathophysiologic characteristics of anorexia and bulimia nervosa. Cerebrospinal fluid neuropeptide Y concentrations were significantly elevated in underweight anorectic patients and in many of the anorectic patients studied at intervals after weight restoration. These levels normalized in long-term weight-restored anorectic patients who had a return of normal menstrual cycles. Increased neuropeptide Y activity may contribute to several characteristic disturbances in anorexia, including menstrual dysregulation. Cerebrospinal fluid peptide YY concentrations were significantly elevated in normal-weight bulimic patients abstinent from pathological eating behavior for a month compared with themselves when actively bingeing and vomiting or compared with healthy volunteers. Increased peptide YY activity may contribute to a drive to overfeed in normal-weight bulimic patients.

Topics: Adult; Anorexia Nervosa; Body Weight; Bulimia; Drive; Eating; Female; Gastrointestinal Hormones; Humans; Menstrual Cycle; Neuropeptide Y; Peptide YY; Peptides

Intestinal tissue mass was significantly reduced throughout the gastrointestinal tract (p less than 0.001) of intravenously fed (TPN) rats. Urogastrone-epidermal growth factor, (URO-EGF), reversed these changes. Although plasma enteroglucagon and gastrin levels showed a small increase with URO-EGF, this was far less than the gut tissue weight change, suggesting that it was unlikely that they were involved in modulating the proliferative response of the intestine to URO-EGF. Peptide tyrosine tyrosine (PYY) levels were however significantly increased by URO-EGF, indicating that PYY may possibly have a role in the modulation of intestinal cell proliferation.

Topics: Animals; Body Weight; Digestive System; Epidermal Growth Factor; Gastrins; Gastrointestinal Hormones; Glucagon-Like Peptides; Male; Organ Size; Parenteral Nutrition, Total; Peptide YY; Peptides; Rats; Rats, Inbred Strains

The relationship between the adaptive response and plasma PYY concentrations after small bowel resection has been investigated. Seventy five per cent proximal small bowel resection resulted in a rise in plasma PYY at six days from 28 +/- 3.1 to 85 +/- 12.3 pmol/l (p less than 0.001) and this difference was maintained to 48 days. Plasma PYY correlates both with crypt cell production rate (CCPR) in the ileum and with plasma enteroglucagon levels. In a second study, PYY or saline was infused over a 12 day period. There were no significant changes in intestinal wet weight or CCPR in any part of the bowel studied. This indicates that it is unlikely that PYY exerts a major trophic effect on the gastrointestinal tract.

Topics: Animals; Body Weight; Cell Division; Chromatography, Gel; Gastrointestinal Hormones; Glucagon-Like Peptides; Intestine, Small; Male; Organ Size; Peptide YY; Peptides; Rats; Rats, Inbred Strains