peptide-yy and Metabolic-Syndrome

The relentless rise in the prevalence of obesity predicts an exponential increase in the incidence of obesity-related complications. Medical and surgical treatments are necessary to prevent and treat obese co-morbidities, thereby avoiding disability and premature death. Interventions for obesity should be evaluated not by weight loss alone but against the new incidence in obesity-related co-morbidities, their remission or improvement. In combination with lifestyle measures, currently available pharmacological therapies -- rimonabant, orlistat and sibutramine -- achieve 5-10% weight loss, although a return to baseline is the norm after cessation of medication. All these agents demonstrate approximately 0.5% reduction in HbA1c in diabetic subjects; orlistat also reduces the new incidence of type 2 diabetes. Modest improvement in lipid profiles and reduced calculated cardiovascular risk is observed, but data on improvement of other co-morbidities are sparse. In contrast, surgical procedures that restrict food ingestion and/or curtail the absorptive surface area of the gut consistently achieve substantial weight loss, typically 20-35%, effect resolution of co-morbid conditions and improve quality of life. Although mortality is low, complications and hospitalisation are not uncommon after bariatric surgery. Intriguingly, surgical patients experience a reduction in appetite and report changes in food preference. Accentuation of the normal gastrointestinal hormonal response to food intake and possible changes in vagal afferent signalling are proposed to induce satiety. Increased understanding of body weight homeostasis and appetite regulation has provided an impressive list of potential targets for drug development, with the promise that single or combination therapy may ultimately challenge the supremacy of bariatric surgery.

Topics: Adipose Tissue; Amyloid; Anticonvulsants; Antidepressive Agents; Anxiety; Appetite Regulation; Bariatric Surgery; Body Mass Index; Bupropion; Cholecystokinin; Ciliary Neurotrophic Factor; Clinical Trials as Topic; Cyclobutanes; Depression; Diabetes Mellitus, Type 2; Female; Fluoxetine; Fructose; Ghrelin; Humans; Intra-Abdominal Fat; Islet Amyloid Polypeptide; Isoxazoles; Lactones; Leptin; Metabolic Syndrome; Metformin; Obesity; Obesity, Morbid; Orlistat; Oxyntomodulin; Peptide YY; Piperidines; Polycystic Ovary Syndrome; Pyrazoles; Rimonabant; Sertraline; Sleep Apnea, Obstructive; Surgical Procedures, Operative; Topiramate; Zonisamide

It has been shown recently that metabolic syndrome is associated with gut dysbiosis. The gut microbiota may be the main target for prevention or treatment of metabolic syndrome. We investigated the effects of synbiotic supplementation on metabolic syndrome. In this triple-blinded clinical trial, 46 Iranian patients with metabolic syndrome, from both sexes, aged 25-70 years, who fulfilled inclusion criteria were randomly categorized to receive either the synbiotic or a placebo capsule, twice a day for three months, plus a weight-loss diet using stratified random sampling based on body mass index (BMI). Each synbiotic capsule consisted of seven strains probiotic bacteria (2× 10

Topics: Adult; Aged; Appetite; Biomarkers; Blood Glucose; Body Mass Index; C-Reactive Protein; Fasting; Female; Humans; Inflammation Mediators; Insulin; Insulin Resistance; Lipids; Male; Metabolic Syndrome; Middle Aged; Peptide YY; Research Design; Synbiotics; Treatment Outcome

The present study investigated the postprandial glycemic and insulinemic responses, the levels of satiety-related proteins, and substrate use after a single dose of a meal replacement (MR) with a high soy protein content and a low glycemic index (GI). The results were compared with a standardized breakfast showing a high GI and a low protein content.. Eleven overweight or obese male subjects with the metabolic syndrome and insulin resistance were included in the study. In the morning, each subject consumed, in a randomized design, 65 g of a MR or an isocaloric standardized breakfast. Four hours after breakfast, all subjects consumed the same standardized lunch. Blood levels of glucose, insulin, ghrelin, protein YY(PYY), oxygen uptake, and carbon dioxide production were determined and the respiratory quotient and substrate use were calculated.. The glycemic and insulinemic responses were considerably higher after the standardized breakfast. In addition, in these obese insulin-resistant subjects, the postprandial decease in fat oxidation was significantly less pronounced after intake of the MR. This effect was also detectable after lunch in terms of a second meal effect. Ghrelin levels were significantly lower 2 h after the intake of the MR and PYY levels tended higher.. Compared with the high GI/low-protein SB, a high soy protein MR with a low GI was associated with lower glycemia and insulinemia and relatively higher fat oxidation in the postprandial period. Together with a favorable course of appetite-regulating hormones, this could further help to explain the beneficial role of MR regimines high in soy protein for weight reduction and improvement of metabolic risk factors.

Topics: Appetite Regulation; Body Mass Index; Diet, Reducing; Energy Intake; Food, Formulated; Ghrelin; Glycemic Index; Humans; Hyperglycemia; Hyperinsulinism; Insulin Resistance; Lipid Metabolism; Male; Metabolic Syndrome; Middle Aged; Obesity; Overweight; Oxygen Consumption; Peptide YY; Postprandial Period; Soybean Proteins

The metabolic syndrome (MS) is a cluster of heterogeneous abnormalities conferring increased risk of cardiovascular diseases. Few postprandial studies have been conducted in MS individuals.. We aimed to study MS subjects with the same abnormalities: abdominal obesity, hypertriglyceridemia and low plasma HDL. We assessed postprandial variations of metabolic parameters related to obesity, dyslipidemia and glucose homeostasis.. In this randomized, double-blind, cross-over study, male MS and control subjects consumed, at separate occasions, a high carbohydrate (HC), high fat (HF) or high protein (HP) breakfast meal providing 30% of each subject's resting energy expenditure.. Appetite hormones peptide YY and ghrelin did not differ between-subject groups. Interleukin-6 was two-fold higher in MS compared with control subjects, consistently with an inflammatory state. Hypertriglyceridemia of MS subjects was aggravated postprandially with the HF and HP meals and was lowest after the HC meal, arguing against increased hepatic VLDL production. HDL-cholesterol of MS subjects remained low postprandially, whereas apolipoprotein (apo) A-II was higher than in control subjects. Unexpectedly, postprandial insulin and glucose responses were higher in MS compared with control subjects, with the HP meal inducing the greater effects.. The sustained postprandial hypertriglyceridemia of MS subjects after all meals suggests defective catabolism of triglyceride-rich lipoproteins. The greater postprandial increases in plasma insulin and glucose in MS relatively to control subjects indicate decreased insulin sensitivity, not revealed in the fasted state.

Topics: Adult; Apolipoprotein A-I; Blood Glucose; Cholesterol, HDL; Cross-Over Studies; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Double-Blind Method; Dyslipidemias; Ghrelin; Humans; Hypertriglyceridemia; Insulin; Interleukin-6; Male; Metabolic Syndrome; Obesity, Abdominal; Peptide YY; Postprandial Period

Metabolic syndrome (MetS) is prevalent among antipsychotic-treated patients; however, in psychiatric clinics, scarce resources often limit the feasibility of monitoring all 5 criteria that are necessary for diagnosing MetS. As one goal of the MetS definition is to facilitate the clinical identification of insulin-resistant individuals, other biomarkers of insulin resistance have been explored. However, there are relatively few data from antipsychotic-treated patients, especially on the association between these markers and the clinical MetS diagnosis.. We analyzed data from 196 psychiatric patients over age 40 years enrolled in an ongoing study of antipsychotic-related metabolic effects that began in August 2005. In addition to anthropometric measures and MetS criteria, levels of certain metabolism-related peptides (ghrelin, adiponectin, peptide YY, leptin, and insulin) were measured. The utility of these clinical and metabolic markers to identify individuals with MetS was evaluated by constructing receiver operating characteristic curves. Optimal cutoff values were calculated for markers with the greatest area under the curve on the basis of sensitivities and specificities for MetS diagnosis.. Ninety-nine subjects (50.5%) met MetS criteria. The receiver operating characteristic analysis found that waist circumference, triglyceride to high-density lipoprotein (TG:HDL) ratio, and body mass index had the greatest area under the curve. The waist circumference cutoff value of 40 inches, TG:HDL ratio of 2.6, and body mass index of 28 kg/m² yielded sensitivities and specificities of 73% and 80%, 74% and 78%, and 75% and 74%, respectively, for MetS diagnosis.. Waist circumference, TG:HDL cholesterol ratio, or body mass index could be used as screens for identifying possible MetS in antipsychotic-treated patients to prompt complete investigation into all MetS criteria.. clinicaltrials.gov Identifier: NCT00245206.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Biomarkers; Body Mass Index; Female; Ghrelin; Humans; Insulin; Leptin; Lipoproteins, HDL; Male; Metabolic Syndrome; Middle Aged; Peptide YY; ROC Curve; Triglycerides; Waist Circumference

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

Various digestive tract procedures effectively improve metabolic syndrome, especially the control of type 2 diabetes mellitus. Very good metabolic results have been shown with vertical gastrectomy and entero-omentectomy; however, the metabolic effects of an isolated entero-omentectomy have not been previously studied.. Nine patients with type 2 diabetes mellitus and a body mass index ranging from 29 to 34.8 kg/m² underwent an entero-omentectomy procedure that consisted of an enterectomy of the middle jejunum and exeresis of the major part of the omentum performed through a mini-laparotomy. Glucagon-like peptide-1 and peptide YY were measured preoperatively and three months following the operation. Fasting and postprandial variations in glycemia, insulinemia, triglyceridemia, hemoglobin A1c, and body mass index were determined in the preoperative period and 3, 18 and, 36 months after the operation.. All patients significantly improved the control of their type 2 diabetes mellitus. Postprandial secretion of peptide YY and Glucagon-like peptide-1 were enhanced, whereas hemoglobin A1c, fasting and postprandial glucose, insulin, and triglyceride levels were significantly reduced. Mean body mass index was reduced from 31.1 to 27.3 kg/m². No major surgical or nutritional complications occurred.. Entero-omentectomy is easy and safe to perform. A simple reduction in jejunal extension and visceral fat causes important improvements in the metabolic profile.

Topics: Adult; Body Mass Index; Diabetes Mellitus, Type 2; Female; Glucagon-Like Peptide 1; Humans; Jejunum; Male; Metabolic Syndrome; Middle Aged; Nutritional Status; Omentum; Peptide YY; Postoperative Period; Time Factors; Treatment Outcome

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

Obesity is a heritable trait that contributes to hypertension and subsequent cardiorenal disease risk; thus, the investigation of genetic variation that predisposes individuals to obesity is an important goal. Circulating peptide YY (PYY) is known for its appetite and energy expenditure-regulating properties; linkage and association studies have suggested that PYY genetic variation contributes to susceptibility for obesity, rendering PYY an attractive candidate for study of disease risk.. To explore whether common genetic variation at the human PYY locus influences plasma PYY or metabolic traits, we systematically resequenced the gene for polymorphism discovery and then genotyped common single-nucleotide polymorphisms across the locus in an extensively phenotyped twin sample to determine associations. Finally, we experimentally validated the marker-on-trait associations using PYY 3'-untranslated region (UTR)/reporter and promoter/reporter analyses in neuroendocrine cells.. Four common genetic variants were discovered across the locus, and three were typed in phenotyped twins. Plasma PYY was highly heritable (P < 0.0001), and genetic pleiotropy was noted between plasma PYY and body mass index (BMI) (P = 0.03). A PYY haplotype extending from the proximal promoter (A-23G, rs2070592) to the 3'-UTR (C+1134A, rs162431) predicted not only plasma PYY (P = 0.009) but also other metabolic syndrome traits. Functional studies with transfected luciferase reporters confirmed regulatory roles in altering gene expression for both 3'-UTR C+1134A (P < 0.001) and promoter A-23G (P = 0.0016).. Functional genetic variation at the PYY locus influences multiple heritable metabolic syndrome traits, likely conferring susceptibility to obesity and subsequent cardiorenal disease.

Topics: 3' Untranslated Regions; Diseases in Twins; Exons; Gene Expression Regulation; Genetic Predisposition to Disease; Genetic Variation; Heart Diseases; Humans; Introns; Kidney Diseases; Metabolic Syndrome; Obesity; Peptide YY; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Twins

Metabolic syndrome (MS), defined as central obesity, hyperinsulinemia, insulin resistance, hypertension, dyslipidemia and glucose intolerance, has been associated with inflammatory biomarkers and cardiovascular diseases. This study was carried out on three groups of women; lean controls, moderately obese with MS (OB-MS) and morbidly obese with MS (MOB-MS). The main objectives were: 1. to analyze the plasma levels of total and acylated ghrelin, peptide YY(3-36) (PYY(3-36)), cholecystokinin (CCK), gastrin and insulin levels under basal conditions and in response to a standard mixed meal, and 2. to elucidate the relationship between the plasma levels of these gut peptides and metabolic syndrome parameters. Plasma levels of the gut hormones were measured by radioimmunoassays at time 0 just before the meal and at 30, 60 and 120 min after a meal ingestion. Traditional lipid profile and high-sensitivity C reactive protein (hs-CRP), the strongest biomarker of inflammation were also determined in OB-MS and MOB-MS. When compared to OB-MS, MOB-MS exhibited much higher anthropometric parameters such as waist circumference, higher fat mass and higher plasma levels of low density lipoprotein-cholesterol (LDL-C) and hs-CRP. Both these obese groups revealed significantly higher values of body mass index (BMI), fat mass, total cholesterol (TC), LDL-C, fasting glucose, fasting insulin, insulin resistance (IR) calculated from homeostatic model assessment (HOMA) and hs-CRP compared to the values recorded in lean subjects. Fasting PYY(3-36) level was lower, while fasting acylated ghrelin was higher in MOB-MS than in OB-MS. Plasma total and acylated ghrelin levels were significantly lower in OB-MS compared to lean women. In MOB-MS women the fasting PYY(3-36) levels were lower compared to lean controls and OB-MS, whilst postprandially in both OB-MS and MOB-MS, it was much lower than in lean women. The fasting plasma levels of total and acylated ghrelin and their postprandial decrease were significantly smaller in both obese groups compared to lean subjects. Plasma hs-CRP levels correlated positively with BMI, waist circumference, fat mass, fasting glucose, HOMA IR and fasting active ghrelin, whilst it negatively correlated with plasma fasting and total ghrelin. Moreover, plasma fasting acylated ghrelin correlated positively with fat mass. Fasting total ghrelin correlated positively with BMI, HDL-C and negatively with HOMA IR. We conclude that MS features of obesity are closely

Topics: Acylation; Adult; Blood Glucose; Body Mass Index; C-Reactive Protein; Cholecystokinin; Cholesterol, LDL; Fasting; Female; Gastrins; Gastrointestinal Hormones; Ghrelin; Humans; Insulin; Insulin Resistance; Metabolic Syndrome; Obesity; Obesity, Morbid; Peptide Hormones; Peptide YY; Poland; Postprandial Period