Inhibition of Food Intake in Obese Subjects by Peptide YY<sub>3–36</sub>

Batterham, Rachel L.; Cohen, Mark A.; Ellis, Sandra; Roux, Carel W. le; Withers, Dominic J.; Frost, Gary; Ghatei, Mohammad A.; Bloom, Stephen R.

doi:10.1056/nejmoa030204

Cited by 1,449 publications

(1,173 citation statements)

References 25 publications

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“…A reduction in plasma ghrelin in the obese A y /a mouse is consistent with the low plasma ghrelin found in obese humans. [37][38][39] The reduction in Arc NPY mRNA expression in obese A y /a mice may contribute to their increased linear growth. Our observation is in contrast to a previous study of obese A y /a mice of a comparable age and body weight that used similar techniques.…”

Section: Discussionmentioning

confidence: 99%

Abnormalities of the somatotrophic axis in the obese agouti mouse

et al. 2005

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Objective: Abnormalities of the melanocortin system produce obesity and increased linear growth. While the obesity phenotype is well characterised, the mechanism responsible for increased linear growth is unclear. The somatotrophic axis was studied in the obese agouti (A y /a) mouse as a model of a perturbed melanocortin system. Design: Adult obese A y /a mice were compared to age-and sex-matched wild-type (WT) controls. Weight and body length (nose-anus) were recorded. Plasma growth hormone (GH), insulin-like growth factor-I (IGFI), insulin and leptin were measured using radioimmunoassay. Since ghrelin is a potent GH secretagogue, plasma ghrelin, stomach ghrelin peptide and stomach ghrelin mRNA expression were studied. Hypothalamic periventricular (PeVN) somatostatin neurones and arcuate (Arc) neuropeptide Y (NPY) neurones inhibit the growth axis, whereas Arc growth hormone-releasing hormone (GHRH) neurones are stimulatory. Therefore, specific hypothalamic expression of somatostatin, NPY and GHRH was measured using quantitative in situ hybridisation. Results: Obese A y /a mice were significantly heavier and longer than WT controls. Plasma IGFI concentrations were 30% greater in obese A y /a mice. Obese A y /a mice were hyperinsulinaemic and hyperleptinaemic, yet plasma ghrelin, and stomach ghrelin peptide and mRNA were significantly reduced. In obese A y /a mice, PeVN somatostatin and Arc NPY mRNA expression were reduced by 50% compared to WT controls, whereas Arc GHRH mRNA expression was unchanged. Conclusion: Increased body length in adult obese A y /a mice may result from reduced Arc NPY and PeVN somatostatin mRNA expression, which in turn, may increase plasma IGFI concentrations and upregulate the somatotrophic axis.

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Section: Discussionmentioning

confidence: 99%

Abnormalities of the somatotrophic axis in the obese agouti mouse

et al. 2005

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“…CCK analysis used Phoenix Peptidese RIA (RK-069-04) for CCK octapeptide (CCK [26][27][28][29][30][31][32][33]. The standard RIA protocol was applied but without extraction of the peptides before the assay.…”

Section: Clinical Indicesmentioning

confidence: 99%

Oat β-glucan supplementation does not enhance the effectiveness of an energy-restricted diet in overweight women

et al. 2009

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Epidemiological evidence shows an inverse relationship between dietary fibre intake and body weight gain. Oat b-glucan, a soluble fibre alters appetite hormones and subjective satiety in acute meal test studies, but its effects have not been demonstrated with chronic consumption. The present study aimed to test the effects in women of two different doses of oat b-glucan on weight loss and hormones associated with appetite regulation. In a 3-month parallel trial, sixty-six overweight females were randomised into one of three 2 MJ energy-deficit diets: a control and two interventions including 5 -6 g or 8 -9 g b-glucan. Anthropometric and metabolic variables (blood glucose level, insulin, total cholesterol (TC), LDL, HDL, TAG and leptin), together with markers of appetite regulation (cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), ghrelin, peptide YY (PYY) and PYY 3-36 ) were measured at baseline and at 3 months. After 3 months, all groups lost weight (P,0·001) and showed a reduced waist circumference (P,0·001). The study sample also showed reductions in TC, LDL, HDL, leptin, PYY, GLP-1 values (all P, 0·001) and an increase in CCK levels (P,0·001). No significant differences were noted between the groups for all outcome values except PYY levels (P¼ 0·018). In broad terms, the addition of oat b-glucan did not enhance the effect of energy restriction on weight loss in mildly overweight women, although wide variations in observed results suggests that individual responsiveness may be an issue. b-D-Glucan: Weight loss: Weight control: Appetite hormonesLarge bodies of epidemiological data show an inverse relationship between dietary fibre intake and body weight (1 -5) so that the logic and simplicity of including fibre in an energy-controlled diet remains tantalising. As a component of food, fibres are found in a fermentable (soluble) or non-fermentable (insoluble) form, but early research has been unable to show benefits from including either form in short term (3 -4 weeks) ad libitum diets (6) . This was also the case when the form of fibre was mixed linkage b-glucan, a soluble fibre delivered by oats (7) , well recognised for its cholesterol (8) and glucose lowering (9) actions. In order to better expose the advantages apparent from epidemiological studies, more work is required in understanding the physical features of fibre, the food delivery system, and how these may work together to affect mechanisms associated with weight management, such as satiety, particularly over longer periods of time.It is accepted that soluble fibre, by its viscous nature will not only increase upper gastrointestinal transit time, but also stimulate cholecystokinin (CCK) that will increase peristalsis (10) . The effects of other hormones are less clear, but the ileal brake formed by undigested foods in the distal gut (occurring with high fibre foods), in addition to the fermentation of soluble fibres in the large bowel are all seen as positive benefits of fibre. Meal studies are able to expose these mechanisms of action. This i...

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“…7 Studies in humans showed that peripheral infusion of postprandial level of PYY into normal and obese subjects decreased the caloric intake at a buffet meal by over 30% in both groups. 7,17 The fasting PYY levels and postprandial PYY release were lower in obese compared to lean individuals. 17 Recently, 101 patients with severe early-onset obesity in the UK were screened for mutations in the PYY and the Y2R genes.…”

Section: Introductionmentioning

confidence: 97%

“…7,17 The fasting PYY levels and postprandial PYY release were lower in obese compared to lean individuals. 17 Recently, 101 patients with severe early-onset obesity in the UK were screened for mutations in the PYY and the Y2R genes. 18 Two PYY SNPs common among both obese and control individuals, and in linkage disequilibrium (LD) with each other, were identified, one being Arg72Thr.…”

Section: Introductionmentioning

confidence: 97%

Common neuropeptide Y2 receptor gene variant is protective against obesity among Swedish men

et al. 2005

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Background: Gut hormones and their receptors are considered important in the control of feeding behavior. The gut hormone peptide-YY (PYY) has anorexic effects via the inhibitory neuropeptide Y2 receptor (Y2R) highly expressed in orexigenic NPY/ AGRP neurons within the arcuate nucleus, a major integrator of appetite control in the hypothalamus. Design: Genetic case-control association study of single nucleotide polymorphisms (SNPs) in Y2R and PYY. Subjects: Swedish Caucasians comprising 148 lean, 129 overweight/obese and 226 morbidly obese men. Measurements: Genotypes of the common, silent and conserved SNP Y2R 585T4C and the common SNP PYY Arg72Thr, as well as various obesity-related clinical parameters. Results: Obese men had a lower allele and homozygosity frequency of the common allele 585T4C:T which was particularly evident comparing morbidly obese with lean men (P ¼ 0.002), and analyzing dependence between continuous body mass index (BMI) and genotype (P ¼ 0.002). In agreement, systolic blood pressure tended to be lower in those homozygous for allele T, which was not explained by the BMI -genotype dependence. We found no association to obesity for the PYY Arg72Thr polymorphism, which is located nearby the essential carboxy terminal. Conclusion: A common and conserved variant of the PYY and NPY receptor Y2R is less prevalent among obese compared to among lean Swedish men. This suggests that the common Y2R variant is protective against obesity. Our findings further implicate Y2R in food intake regulation.

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Inhibition of Food Intake in Obese Subjects by Peptide YY_3–36

Abstract: We found that obese subjects were not resistant to the anorectic effects of PYY. Endogenous PYY levels were low in the obese subjects, suggesting that PYY deficiency may contribute to the pathogenesis of obesity.

Cited by 1,449 publications

References 25 publications

Abnormalities of the somatotrophic axis in the obese agouti mouse

Abnormalities of the somatotrophic axis in the obese agouti mouse

Oat β-glucan supplementation does not enhance the effectiveness of an energy-restricted diet in overweight women

Common neuropeptide Y2 receptor gene variant is protective against obesity among Swedish men

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Inhibition of Food Intake in Obese Subjects by Peptide YY3–36

Abstract: We found that obese subjects were not resistant to the anorectic effects of PYY. Endogenous PYY levels were low in the obese subjects, suggesting that PYY deficiency may contribute to the pathogenesis of obesity.

Cited by 1,449 publications

References 25 publications

Abnormalities of the somatotrophic axis in the obese agouti mouse

Abnormalities of the somatotrophic axis in the obese agouti mouse

Oat β-glucan supplementation does not enhance the effectiveness of an energy-restricted diet in overweight women

Common neuropeptide Y2 receptor gene variant is protective against obesity among Swedish men

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Inhibition of Food Intake in Obese Subjects by Peptide YY_3–36