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.

Ghrelin is a recently identified endogenous ligand for the growth hormone secretagogue receptor. It is synthesized predominantly in the stomach and found in the circulation of healthy humans. Ghrelin has been shown to promote increased food intake, weight gain and adiposity in rodents. The effect of ghrelin on appetite and food intake in man has not been determined. We investigated the effects of intravenous ghrelin (5.0 pmol/kg/min) or saline infusion on appetite and food intake in a randomised double-blind cross-over study in nine healthy volunteers. There was a clear-cut increase in energy consumed by every individual from a free-choice buffet (mean increase 28 ± 3.9%, p<0.001) during ghrelin compared with saline infusion. Visual analogue scores for appetite were greater during ghrelin compared to saline infusion. Ghrelin had no effect on gastric emptying as assessed by the paracetamol absorption test. Ghrelin is the first circulating hormone demonstrated to stimulate food intake in man. Endogenous ghrelin is a potentially important new regulator of the complex systems controlling food intake and body weight. _____________________________________________________________________________________________________

No abstract

Exendin-4 reduces fasting and postprandial glucose and decreases energy intake in healthy volunteers. Am J Physiol Endocrinol Metab 281: E155-E161, 2001.-Exendin-4 is a long-acting potent agonist of the glucagon-like peptide 1 (GLP-1) receptor and may be useful in the treatment of type 2 diabetes and obesity. We examined the effects of an intravenous infusion of exendin-4 (0.05 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) compared with a control saline infusion in healthy volunteers. Exendin-4 reduced fasting plasma glucose levels and reduced the peak change of postprandial glucose from baseline (exendin-4, 1.5 Ϯ 0.3 vs. saline, 2.2 Ϯ 0.3 mmol/l, P Ͻ 0.05). Gastric emptying was delayed, as measured by the paracetamol absorption method. Volunteers consumed 19% fewer calories at a free-choice buffet lunch with exendin-4 (exendin-4, 867 Ϯ 79 vs. saline 1,075 Ϯ 93 kcal, P ϭ 0.012), without reported side effects. Thus our results are in accord with the possibility that exendin-4 may be a potential treatment for type 2 diabetes, particularly for obese patients, because it acts to reduce plasma glucose at least partly by a delay in gastric emptying, as well as by reducing calorie intake.glucagon-like peptide 1; glycemia; gastric emptying; type 2 diabetes GLUCAGON-LIKE PEPTIDE 1 (GLP-1) is released from the intestine in response to nutrient ingestion (20). Exogenous administration to humans has a number of effects that result in a decrease in plasma glucose levels. It stimulates plasma insulin levels (20), suppresses glucagon levels (22), and delays gastric emptying (27,45). There is some evidence that GLP-1 may also increase peripheral insulin sensitivity (4, 16), although this is controversial (30). GLP-1 has been shown to decrease food intake and body weight in rats when administered into the third cerebral ventricle (24,42). A number of groups have looked at the effect of GLP-1 on satiety and food intake in humans, and it appears to parallel the effect seen in rats, although not always (11,18,23,25). Recently, we infused the GLP-1 antagonist, exendin-(9-39), in humans and demonstrated that endogenous GLP-1 regulates plasma glucose levels (10), and its effects on plasma glucagon and gastric emptying appear to be physiological (10). GLP-1 has also been shown to have a physiological role in glucose homeostasis in the rat (21, 44), mouse (38), and baboon (5), although it appears that this is not always the case, as exogenous administration has little effect in the calf (9).Exendin-4 is a 39-amino acid peptide isolated from the Gila monster salivary gland and acts as an agonist of the GLP-1 receptor (13, 40). Exendin-4 appears to have a considerably greater biological half-life than GLP-1 (14, 39, 46). We (10) have shown that the circulating half-life of the truncated exendin-4, exendin-(9-39), is 33 Ϯ 4 min in humans; this compares with a half-life for the biologically active intact GLP-1 of 1-3 min in a number of species (6,19,32). Thus it would appear likely that exendin-4 has a longer circulating and biological half-life than GLP-1 in hu...

In this study we assessed different magnetic resonance imaging (MRI) scanning regimes and examined some of the assumptions commonly made for measuring body fat content by MRI. Whole body MRI was used to quantify and study different body fat depots in 67 women. The whole body MRI results showed that there was a significant variation in the percentage of total internal, as well as visceral, adipose tissue across a range of adiposity, which could not be predicted from total body fat and/or subcutaneous fat. Furthermore, variation in the amount of total, subcutaneous, and visceral adipose tissue was not related to standard anthropometric measurements such as skinfold measurements, body mass index, and waist-to-hip ratio. Finally, we show for the first time subjects with a percent body fat close to the theoretical maximum (68%). This study demonstrates that the large variation in individual internal fat content cannot be predicted from either indirect methods or direct imaging techniques, such as MRI or computed tomography, on the basis of a single-slice sampling strategy.