Endocrine Abstracts

The gastrointestinal-derived hormone peptide YY (PYY) is released from intestinal L-cells post-prandially in proportion to calorie intake, and modulates food intake. Peripheral administration of PYY (3-36) reduces food intake and body weight in rodents and suppresses appetite and food intake in humans. PYY(3-36) is hypothesised to inhibit food intake via activation of the auto-inhibitory pre-synaptic neuropeptide Y (NPY) Y2 receptor (Y2R) present on arcua...

The melanocortin receptors (MCR), MC3R and MC4R, have established roles in feeding and pituitary function. MC5R mRNA expression has been identified at low levels in the hypothalamus. However, a role for this receptor in appetite and pituitary function remains to be elucidated. We investigated the effects of central administration of an MC5R agonist (3,3,3-triphenylpropionyl-His-D-Phe-Arg-Trp-NH2) on food intake and plasma pituitary hormone levels. We did not observe...

The hypothalamic melanocortin system consists of an endogenous antagonist, agouti related protein (Agrp) and agonist, alpha-melanocyte stimulating hormone (alpha-MSH), which act at the hypothalamic melanocortin 3 and 4 receptors. CNS administration of Agrp increased food intake over a 24-h period. Agrp blocked the reduction in 1-h food intake observed following alpha-MSH administration. This effect occurred independently of whether the antagonist was administered simultaneousl...

Peptide YY(3-36) (PYY(3-36)) is secreted from endocrine L-cells of the gastrointestinal tract and is thought to induce post-prandial satiety by inhibiting the release of neuropeptide Y (NPY) in the arcuate nucleus of the hypothalamus via the hypothalamic neuropeptide Y2 receptor (Y2R). NPY mRNA expression in the hypothalamus is markedly increased with fasting. Therefore, we investigated the effect of intraperitoneal (i.p.) injections of PYY(3-36) (120ug/kg) on food intake vers...

The CNS and gut derived peptide Neuromedin U (NMU) has been shown to inhibit feeding following intracerebroventricular (ICV) injection. The present study aimed to further explore the hypothalamic actions of NMU. ICV NMU-23 (1nmol), but not truncated NMU-8, significantly inhibited feeding (1h food intake: 3.8 plus/minus 0.4g vs saline 5.4 plus/minus 0.6g, p <0.05). Following micro-injection into 8 hypothalamic areas, NMU-23 potently inhibited feeding in the PVN (1h food int...

The gastric hormone ghrelin stimulates feeding whereas the intestinal hormones peptide YY3-36 (PYY3-36) and oxyntomodulin inhibit feeding. In order to determine whether these gut hormones retain their effects in obesity, they were administered in vivo intraperitoneally to unanaesthetised lean and obese mice. Forty eight C57Bl/6 male mice were randomised to receive either low-fat diet (4.5% fat) or high fat diet (60% fat). After 16 weeks, mice fed o...

The gastric hormone ghrelin increases appetite and energy intake when administered by intravenous infusion to human subjects and has recently been reported to increase energy intake in patients with anorexia of cancer. Ghrelin also stimulates growth hormone release. We have now investigated whether subcutaneous administration of ghrelin is effective. Approval of the local ethics committee was obtained. Following a preliminary dose-finding study, 16 lean healthy volunteers rece...

In addition to obesity, models of abnormal hypothalamic melanocortin signalling display increased linear growth, although the mechanism remains unclear. We have studied the somatotrophic axis in the obese agouti (Ay/a) mouse (male, 12-14 weeks), as a model of an altered melanocortin system. Somatotrophic hormones were measured by radioimmunoassay and hypothalamic neuropeptide expression studied by in situhybridisation.Obese A<...

Ghrelin, a circulating gastric hormone, stimulates food intake in rodents and humans and hyperphagia, weight gain and adiposity on chronic administration in rodents. Here we investigated the effect of chronic subcutaneous ghrelin on fat volume and distribution using magnetic resonance imaging (MRI). Male Wistar rats were implanted with subcutaneous osmotic mini-pumps delivering saline (S, n=10) or ghrelin 30nmol/24hours (n=18). In order to investigate the hyperphagia-independe...

Hypothalamic Cocaine- and Amphetamine-regulated transcript (CART) is regulated by circulating glucocorticoids. In adrenalectomised rodents, CART expression is reduced in the arcuate nucleus. However, CART also modulates the hypothalamo-pituitary-adrenal (HPA) axis. Acute intracerebroventricular injection of CART peptide significantly increases plasma ACTH and corticosterone but the long-term actions of CART are unknown. The aim of these studies was to determine the effect of l...