Neuropeptide Y concentrations in cerebrospinal fluid are unchanged in obesity

Neuropeptide Y (NPy) is a potent centrally acting appetite-stimulating peptide implicated in the regulation of energy balance. It induces hyperphagia and obesity when injected into the rat hypothalamus. Hypothalamic NPY and NPY mRNA levels are increased in spontaneously obese rats, suggesting that it may be involved in causing obesity in rodents. It is not known whether NPY has a role in the pathogenesis of obesity in man. NPY is found in human cerebrospinal fluid (CSF) and we have therefore compared CSF NPY levels in normal obese and non-obese individuals to determine whether NPY concentrations might be increased in obesity. We studied 25 clinically normal subjects (age 67 ± 5 years. male 11. female 14) undergoing spinal anaesthesia. None had any significant illness. Samples of 1 ml were freeze-dried and reconstituted to 100 ul and 35ul aliquots were assayed for NPY using an in-house RIA. CSF NPY levels were not correlated with body mass index (BMI) (r=O.088. p=O.673) and there were no differences in NPY concentrations between groups of subjects stratified for BMI: BMI 25 (n=ll), 702 ± 55 fmol/ml (differences between all groups. p>0l). CSF NPY levels are therefore not increased in human obesity. NPY is found in many brain regions outside the hypothalamic appetite-regulating nuclei, which could contribute to CSF levels. This negative observation does not therefore exclude a role of the peptide, acting specifically in the hypothalamus, in contributing to human obesity

Alterations in neuropeptide Y levels in the hypothalamus of the rat following treatment with methysergide

Methysergide (Meth) is a non selective 5-HT antrtgonist which stimulates feeding in rats. 5-HT has been suggested to induce satiety. Neuropeptide Y (NPY) is a 36 amino-acid peptide sbucturally related to pancreatic polypeptide, and one of the most abundant neuropeptide in the brain.\ud \ud 5-HT fibres project to the hypothalamus particularly the paravenmcular(PVN) and arcuatc (ARC) nuclei, sites of NPY action and synthesis respectively.\ud \ud This study set out to examine the effect of acute and chronic adminisnation of methysergide on hypothalamic NPY. Male Wistar rats were used. In the acute experiment, rats were injected with either saline (0.9% n=8) or methysergide(l0mgkg n=8) and killed after four hours.\ud \ud In the chronic experiment, rats were implanted with mini-osmotic pumps filled with either saline (n=8) or methysergide (lOmg/kg/day n=8). Rats were killed after seven days.\ud \ud Food intake was greater in the methysergide treated rats after four hours compared with the saline treated rats p<0.01).\ud \ud NPY levels were significantly increased in the PVN and ARC in the methysergide treated rats (PVN 61± 3.2 vs 47± 3 fmoUug protein p<O.OI. ARC 49± 4.2 vs 27± 3.2 pcO.01).\ud \ud In the chronically mated rats food intake was raised by 13% over seven days (p<O.01).\ud \ud Again NPY levels were significantly increased in the methysergide treated rats (PVN 66± 6.2 vs 47± 3.1 fmo/ug protein p=O.Ol. ARC 38.5 ± 3 vs 27.4± 3.2 p=0.02).\ud \ud These results suggest that methysergide induced feeding is associated with changesin NPYergic activity in critical hypothalamic areas

The vitamin K-dependent Gla proteins and risk of type 2 diabetes

[Extract] Recently Haase et al [1] reported that maternal low-protein diet in rats was associated with decreased beta cell mass and decreased expression of growth arrest specific protein 6 (GAS6) in islets of Langerhans, and that incubation of neonatal islets with GAS6 enhanced beta cell proliferation. Low beta cell mass early in life is associated with increased future risk of type 2 diabetes. Consistent with a protective effect of GAS6, the c.834+7G>A polymorphism is associated with type 2 diabetes risk in humans [2]. The AA phenotype is associated with higher levels of GAS6, lower glucose levels, and decreased diabetes risk. Currently used drugs affecting the incretin axis have stimulated interest in therapeutic approaches that either preserve or enhance beta cell mass or function, and GAS6 (secreted by alpha cells) is, therefore, an attractive therapeutic target