neuropeptide-y and Overweight

We are currently facing an obesity pandemic, with worldwide obesity rates having tripled since 1975. Obesity is one of the main risk factors for the development of non-communicable diseases, which are now the leading cause of death worldwide. This calls for urgent action towards understanding the underlying mechanisms behind the development of obesity as well as developing more effective treatments and interventions. Appetite is carefully regulated in humans via the interaction between the central nervous system and peripheral hormones. This involves a delicate balance in external stimuli, circulating satiating and appetite stimulating hormones, and correct functioning of neuronal signals. Any changes in this equilibrium can lead to an imbalance in energy intake versus expenditure, which often leads to overeating, and potentially weight gain resulting in overweight or obesity. Several lines of research have shown imbalances in gut hormones are found in those who are overweight or obese, which may be contributing to their condition. Therefore, this review examines the evidence for targeting gut hormones in the treatment of obesity by discussing how their dysregulation influences food intake, the potential possibility of altering the circulating levels of these hormones for treating obesity, as well as the role of short chain fatty acids and protein as novel treatments.

Topics: Acetic Acid; Animals; Appetite; Appetite Regulation; Butyrates; Central Nervous System; Cholecystokinin; Dipeptides; Energy Intake; Energy Metabolism; Fatty Acids, Volatile; Gastrointestinal Hormones; Gastrointestinal Tract; Ghrelin; Glucagon-Like Peptide 1; Humans; Hyperphagia; Mice; Neuropeptide Y; Obesity; Overweight; Oxyntomodulin; Pancreatic Polypeptide; Propionates; Satiation

Effects of dietary fiber on obesity-related traits in previous studies were inconsistent. The aim of the present study was to explore whether variants in genes related to satiety and appetite can modulate the effect of dietary fiber on obesity-related traits. Fifty-one overweight or obese adults were randomly allocated to two groups to consume control biscuits (n = 24) or biscuits containing defatted flaxseed flour (n = 27) at breakfast for 8 wk. Four single-nucleotide polymorphisms related to satiety and appetite were genotyped: rs11076023 on the FTO gene, rs16147 on the NPY gene, rs155971 on the PCSK1 gene, and rs6265 on the BDNF gene. A linear regression model was used to evaluate the gene-diet interaction between obesity-related traits. Compared with control biscuits, defatted flaxseed-flour biscuits significantly reduced body weight (P = 0.001) and body mass index (BMI) (P = 0.001) in A-allele carriers (AA + AT) of rs11076023 on the FTO gene but not in non-carriers (TT) (P for the interaction = 0.005 and 0.006) and decreased fasting serum glucose in participants with CC genotype (P = 0.019) but had less effect in T-allele carriers (TT + TC) (P = 0.021) of rs16147 on the NPY gene (P for the interaction = 0.002). Compared with the control biscuits, defatted flaxseed flour significantly reduced body weight (P < 0.001) in T-allele carriers (TT + TC) of rs155971 on the PCSK1 gene but not in non-carriers (CC) (P for the interaction = 0.041) and reduced body weight (P = 0.001) and BMI (P < 0.001) in A-allele carriers (AA + AG) of rs6265 on the BDNF gene but not non-carriers (GG) (P for the interaction = 0.017 and 0.018). Variants of genes related to satiety and appetite could modulate the effect of defatted flaxseed flour on obesity-related traits.

Topics: Adult; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Body Mass Index; Body Weight; Brain-Derived Neurotrophic Factor; China; Diet; Dietary Fiber; Dietary Supplements; Flax; Flour; Genotype; Humans; Neuropeptide Y; Obesity; Overweight; Polymorphism, Single Nucleotide; Seeds

Grape seed extract (GSE) is a natural supplement known for its various health benefits, including anti-inflammatory effect. This study aimed to evaluate the effects of GSE supplementation on inflammatory markers, neuropeptide Y, anthropometric measurements, and appetite in obese or overweight individuals.. A randomized, double-blind clinical trial was performed on 40 obese or overweight subjects who were randomly assigned to receive GSE (300 mg/day) or placebo for a period of 12-weeks. Both groups were under a restricted calorie diet (RCD)(~250 kcal lower than the estimated energy requirement). Anthropometric measurements, biochemical biomarkers and dietary intakes were determined during the study period.. The reductions of body weight, body mass index, waist circumference, and waist to hip ratio were significantly higher in the GSE group compared to the placebo group (P = 0.045, 0.033, 0.029, and 0.021, respectively). Lower levels of neuropeptide Y, tumor necrosis factor alpha, and high sensitivity C-reactive protein were observed in the GSE group in comparison with the placebo group (P = 0.041, 0.001, and 0.034, respectively).. GSE supplement with a RCD has favorable effects in reducing anthropometric measurements and inflammatory markers in obese or overweight individuals, and may play an effective role in the treatment of obesity.

Topics: Adult; Appetite; Biomarkers; Body Mass Index; Body Weight; C-Reactive Protein; Caloric Restriction; Dietary Supplements; Double-Blind Method; Female; Grape Seed Extract; Humans; Inflammation; Male; Neuropeptide Y; Obesity; Overweight; Vitis; Waist Circumference; Waist-Hip Ratio

Neuropeptide Y (NPY) is implicated in the regulation of blood pressure (BP), and NPY pathways in the hypothalamus are sensitive to dietary fat. We evaluated the potential effect of a functional variant rs16147 located in the NPY gene promoter region on the association between 2-year diet intervention and change in multiple BP measures in the randomized Preventing Overweight Using Novel Dietary Strategies Trial. The NPY rs16147 was genotyped in 723 obese adults who were randomly assigned to 1 of 4 diets differing in the target percentages of energy derived from fat, protein, and carbohydrate. The changes of 4 BP phenotypes, including systolic BP, diastolic BP, pulse pressure, and mean arterial pressure, during 2-year diet intervention were analyzed. In the total participants and participants with hypertension, we observed significant and consistent interactions between rs16147 genotype and dietary fat intake on changes in multiple BP phenotypes at 2 years (all P for interactions <0.05). The risk allele (C allele) was associated with a greater reduction of BP phenotypes in response to low-fat diet, whereas an opposite genetic effect was observed in response to high-fat diet. In addition, the C allele was related to greater changes in 4 BP phenotypes in hypertensive compared with nonhypertensive participants. Our data suggest that NPY rs16147 may modulate the association between dietary fat intake and changes in BP phenotypes, and the C allele exerts a long-term beneficial effect on lowering BP in response to low-fat diet in obese and hypertensive subjects.

Topics: Adult; Alleles; Blood Pressure; Diet, Reducing; Female; Gene Frequency; Genotype; Humans; Male; Middle Aged; Neuropeptide Y; Obesity; Overweight; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Time Factors; Treatment Outcome

Topics: Abdominal Fat; Adaptor Proteins, Signal Transducing; Adipogenesis; Adult; Adult Stem Cells; Apoptosis Regulatory Proteins; Biomarkers; CCAAT-Enhancer-Binding Proteins; Cell Proliferation; Cells, Cultured; Elective Surgical Procedures; Female; Gene Expression Regulation, Developmental; Humans; Lipid Droplets; Lipid Metabolism; Neuropeptide Y; Nuclear Proteins; Nuclear Receptor Interacting Protein 1; Osmolar Concentration; Overweight; PPAR gamma; Proteins; Receptors, Neuropeptide Y

Food structure contributes to the induction of satiation and the maintenance of satiety following intake of a meal. There is evidence from human studies that protein-crosslinking of a milk-protein based meal may enhance satiety, but the mechanism underpinning this effect is unknown. We investigated whether a rat model would respond in a similar manner and might provide mechanistic insight into enhanced satiety by structural modification of a food source. Rats were schedule fed a modified AIN-93M based diet in a liquid form or protein-crosslinked to produce a soft-solid form. This was compared to a modified AIN-93M solid diet. Average daily caloric intake was in the order solid > liquid > crosslinked. Body composition was unaltered in the solid group, but there was a loss of fat in the liquid group and a loss of lean and fat tissue in the crosslinked group. Compared to rats fed a solid diet, acute responses in circulating GLP-1, leptin and insulin were eliminated or attenuated in rats fed a liquid or crosslinked diet. Quantification of homeostatic neuropeptide expression in the hypothalamus showed elevated levels of Npy and Agrp in rats fed the liquid diet. Measurement of food intake after a scheduled meal indicated that reduced energy intake of liquid and crosslinked diets is not due to enhancement of satiety. When continuously available ad-libitum, rats fed a liquid diet showed reduced weight gain despite greater 24 h caloric intake. During the dark phase, caloric intake was reduced, but compensated for during the light phase. We conclude that structural modification from a liquid to a solidified state is beneficial for satiation, with less of a detrimental effect on metabolic parameters and homeostatic neuropeptides.

Topics: Agouti-Related Protein; Animals; Diet, Reducing; Energy Intake; Food Handling; Gene Expression Regulation; Glucagon-Like Peptide 1; Hypothalamus; Insulin; Insulin Secretion; Leptin; Male; Milk Proteins; Neurons; Neuropeptide Y; Overweight; Rats, Sprague-Dawley; Satiety Response; Transglutaminases; Weight Gain; Weight Loss

Over the past decades, life-styles changing have led to exacerbated food and caloric intake and a reduction in energy expenditure. Obesity, main outcome of these changes, increases the risk for developing type 2 diabetes, cardiovascular disease and metabolic syndrome, the leading cause of death in adult and middle age population. Body weight and energy homeostasis are maintained via complex interactions between orexigenic and anorexigenic neuropeptides that take place predominantly in the hypothalamus. Overeating may disrupt the mechanisms of feeding control, by decreasing the expression of proopiomelanocortin (POMC) and α-melanocyte stimulating hormone (α-MSH) and increasing orexigenic neuropeptide Y (NPY) and agouti-related peptide (AgRP), which leads to a disturbance in appetite control and energy balance. Studies have shown that regular physical exercise might decrease body-weight, food intake and improve the metabolic profile, however until the currently there is no consensus about its effects on the expression of orexigenic/anorexigenic neuropeptides expression. Therefore, we propose that the type and length of physical exercise affect POMC/αMSH and NPY/AgRP systems differently and plays an important role in feeding behavior. Moreover, based on the present reports, we hypothesize that increased POMC/αMSH overcome NPY/AgRP expression decreasing food intake in long term physical exercise and that results in amelioration of several conditions related to overweight and obesity.

Topics: Agouti-Related Protein; alpha-MSH; Animals; Appetite Regulation; Body Weight; Eating; Energy Metabolism; Exercise; Feeding Behavior; Humans; Hypothalamus; Models, Theoretical; Neuropeptide Y; Neuropeptides; Obesity; Overweight; Pro-Opiomelanocortin

The role of neuropeptide Y (NPY) and its gene polymorphisms in the development of atherosclerosis has become increasingly evident. In asthma, NPY has been shown to be involved as immunomodulator. In this study, we investigated the role of two functional NPY polymorphisms, NPY-Leu7Pro (rs16139) and NPY-399C/T (rs16147) and obesity for the development of asthma as well as atherosclerosis in asthmatic and non-asthmatic subjects. Also, we measured heart rate variability (HRV) and NPY in serum since these might contribute through these polymorphisms to both diseases.. Thousand hundred and seventy six Finnish young adults were genotyped and three groups (G1-G3) were formed based on the observed diplotypes. The NPY-Pro7 allele always co-existed with the NPY-399T allele indicating complete linkage disequilibrium. Here we show that overweight (BMI≥25kg/m2) was associated with 2.5-fold increased risk for asthma in subjects with the NPY-399T allele without NPY-Pro7 allele (G2, n=716). Overweight was also associated with increased atherosclerosis determined by carotid intima media thickness (cIMT), but asthma seemed to be more significant determinant than overweight in determing cIMT having a decreasing effect. NPY concentration in serum was diplotype-driven (G1=792.2(29.5), G2=849.0(18.9), G3=873.9(45.2) pg/ml) and correlated positively with cIMT in the group having NPY-Pro7 allele (G3, n=142). However, the subjects with asthma had a negative NPY-cIMT relationship. Total HRV was increased in asthma and correlated negatively with cIMT irrespective of the NPY genotype.. Overweight together with the NPY-399T allele without NPY-Pro7 allele was associated with increased risk for asthma. Atherosclerosis was decreased in subjects with asthma depending on the NPY genotype. The results reveal novel insights into the genetics and biology of the relationship of atherosclerosis and asthma.

Topics: Adolescent; Alleles; Anthropometry; Asthma; Atherosclerosis; Body Height; Body Weight; Carotid Intima-Media Thickness; Child; Child, Preschool; Cohort Studies; Data Interpretation, Statistical; DNA; Endothelium, Vascular; Female; Finland; Gene Frequency; Genotype; Heart Rate; Humans; Lipids; Male; Neuropeptide Y; Overweight; Polymorphism, Genetic; Risk

The present study explored the effects of early and post-weaning malnutrition and nutritional rehabilitation on orexigenic (orexin (ORX) and neuropeptide Y (NPY)) and anorexigenic peptides (alpha-melanocyte stimulating hormone (alpha-MSH)) expressed in hypothalamic nuclei. Male Wistar rats were malnourished during gestation-lactation (MGL) or from weaning to post-natal day 55 (MPW; P55). Two groups of rats were rehabilitated with a balanced diet until P90 (MGL-R and MPW-R, respectively). After a glucose tolerance test (GTT) brains were processed for immunohistochemistry. Malnourished groups were hyperglycemic after GTT. ORX expression did not display any difference. Only MGL rats showed increased NPY immunoreactivity in ARC and PVN nuclei, and both malnourished groups showed low alpha-MSH expression in the PVN and DMH, as compared with their controls. After nutritional rehabilitation rats showed normal GTT, increased rate of body and adipose tissue weights and high proportion of food ingestion. Both rehabilitated groups maintained low alpha-MSH expression in the PVN, indicating a deleterious long-lasting effect.

Topics: alpha-MSH; Animals; Female; Glucose Tolerance Test; Hyperglycemia; Hypothalamus; Immunohistochemistry; Intracellular Signaling Peptides and Proteins; Lactation; Male; Malnutrition; Mediodorsal Thalamic Nucleus; Neurons; Neuropeptide Y; Neuropeptides; Orexins; Overweight; Rats; Rats, Wistar; Weaning

To compare whether serum lipids and their changes during a health education intervention are associated with the Leu7Pro polymorphism in the signal peptide part of neuropeptide Y (NPY) in children with normal weight and in those with overweight.. An intervention study.. A family-based intervention of risk factors for prevention of CHD in Finland.. Subjects were 443 children with a family history of CVD participating in family-based health education. The children were divided into two groups according to NPY genotype: children with Leu7/Pro7 or Pro7/Pro7 genotype (n 50) and children with Leu7/Leu7 genotype (n 393). The final sample of the follow-up study included 353 (80 %) children (Pro7 allele carriers, n 43; Leu7/Leu7, n 310).. At baseline, the Leu7Pro polymorphism was not associated with serum lipid values after adjustment for body weight in boys or girls. There was a significant interaction of NPY genotype group by time and body weight (P = 0.043 for three-way interaction: time x NPY genotype x body weight) in LDL-cholesterol (LDL-C) concentration among boys. LDL-C decreased among boys with normal weight in both NPY groups and in overweight boys with the Leu7/Leu7 genotype, whereas it increased in overweight boys with the Pro7 allele. Two-way interaction (time x NPY genotype) showed no significant differences in changes of serum lipids between the NPY genotype groups among boys or girls.. The Leu7Pro polymorphism may be associated with dietary response to LDL-C concentration in overweight boys with a family history of early-onset CVD.

Topics: Adolescent; Adolescent Nutritional Physiological Phenomena; Alleles; Cardiovascular Diseases; Child; Child Nutritional Physiological Phenomena; Cholesterol, LDL; Female; Finland; Genetic Predisposition to Disease; Genotype; Health Education; Humans; Leucine; Lipids; Male; Neuropeptide Y; Overweight; Polymorphism, Genetic; Proline; Public Health; Risk Factors; Sex Factors; Thinness

To studied the relationship that exists between leptin, ghrelin, insulin, neuropeptide Y (NPY), anthropometric, and metabolic variables in Saudi females.. The study was conducted at the Department of Genetics, King Faisal Specialist Hospital & Research Center, Riyadh, Kingdom of Saudi Arabia from November 2004 to August 2005. One hundred and twenty-two Saudi females were divided into 3 body mass index (BMI) groups: lean (N=60), overweight (N=17), and obese (N=45). Fasting leptin, ghrelin, insulin, NPY and glucose concentrations were determined.. Leptin levels in overweight and obese groups were significantly higher than those in lean group. Leptin levels showed a positive correlation with BMI in obese (0.81), overweight (0.78), and lean (0.48). In contrast, ghrelin concentration decreased in obese and overweight subjects compared to lean subjects. Ghrelin levels were negatively correlated with BMI in obese (-0.81), overweight (-0.58), and lean subjects (-0.62). Negative correlations were found between serum insulin and ghrelin concentrations in lean and obese subjects. Glucose and insulin levels were significantly higher in the obese group compared to controls. No differences were found in serum NPY between the 3 groups.. Leptin levels increased remarkably with increasing BMI. A leptin resistance state seems to exist in many obese and overweight individuals. Ghrelin concentration was decreased in overweight and obese subjects. These data demonstrate a significant inverse relationship between ghrelin and leptin levels in overweight and obese subjects.

Topics: Adult; Body Mass Index; Case-Control Studies; Female; Ghrelin; Humans; Insulin; Leptin; Neuropeptide Y; Obesity; Overweight; Peptide Hormones; Saudi Arabia

To investigate the association between DNA polymorphisms in the NPY and AGRP genes and body fatness.. The association between the AGRP Ala67Thr or the NPY Leu7Pro polymorphisms and indicators of body fatness (baseline leptin levels, body mass index (BMI) values and prevalence of overweight) are investigated in 582 participants of two large cohorts in The Netherlands (total 18 500 adult men and women), aged 20-40 years whose weight remained relatively constant or whose weight increased substantially (range 5.5-47 kg) during a mean follow-up of 7 years.. No consistent associations were found for the indicators of body fatness for men and women. Among women, BMI values, leptin levels and prevalence of overweight were not statistically different for carriers of the mutant alleles compared to that of the non-carriers. Among men, carriers of the Thr67-allele of the AGRP gene had similar leptin levels, but higher BMI values compared to those with the genotyping Ala67/Ala67: mean adjusted BMI 25.6 kg/m2 (95% CI 24.3-27.0) vs 23.9 kg/m2 (23.6-24.3). Also, the risk of being overweight at baseline tended to be higher for male carriers of the Thr67-allele of the AGRP gene (OR 2.52; 95% CI 0.86-7.4). Furthermore, male carriers of the Pro7-allele of the NPY gene had on average higher leptin levels and BMI values vs non-carriers of this allele: 4.7 microg/l (95% CI 3.7-6.0) and 25.7 kg/m2 (95% CI 24.4-27.0) vs 3.1 microg/l (95% CI 2.9-3.4) and 23.9 kg/m2 (95% CI 23.5-24.3), respectively. These male carriers had also a higher risk on being overweight at baseline (OR 3.3 (95% CI 1.2-8.9)) compared to non-carriers of the Pro7-allele.. The consistent findings among men suggest that the NPY Leu7Pro polymorphism (or another linked marker) might be involved in the development of obesity at younger ages. The findings for the AGRP Ala67Thr were less consistent and need further investigation. Among women, these polymorphisms do not play an important role.

Topics: Adult; Agouti-Related Protein; Anthropometry; Body Mass Index; Cohort Studies; Female; Genotype; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Male; Neuropeptide Y; Overweight; Polymorphism, Genetic; Weight Gain