Ghrelin and PYY(3-36) in gastrectomized and vagotomized patients: relations with appetite, energy intake and resting energy expenditure.

BACKGROUND/OBJECTIVES: Reduced food intake, appetite loss and alteration of ghrelin and PYY(3-36) secretion have been suggested to have a function in the loss of body weight commonly observed after gastrectomy. The objective of this study was to investigate the circulating concentrations of ghrelin and PYY(3-36) and their relationships with food intake, appetite and resting energy expenditure (REE) after gastrectomy plus vagotomy. SUBJECTS/METHODS: Seven patients with total gastrectomy (TG), 14 with partial gastrectomy (PG) and 10 healthy controls were studied. Habitual food intake and REE was assessed; fasting and postprandial plasma total ghrelin, PYY(3-36) concentrations and appetite ratings were determined after ingestion of a liquid test meal. RESULTS: Differently from PG and controls, fasting ghrelin correlated with REE, and a higher energy intake was observed in the TG group. Fasting plasma ghrelin concentrations were lower in TG compared with controls, and no ghrelin response to the meal was observed in either PG or TG. Fasting plasma PYY(3-36) concentrations were not different among the groups. There was an early and exaggerated postprandial rise in PYY(3-36) levels in both PG and TG groups, but not in controls. No effect of ghrelin or PYY(3-36) concentrations was observed on hunger, prospective consumption or fullness ratings. CONCLUSIONS: Total ghrelin and PYY(3-36) do not seem to be involved with appetite or energy intake regulation after gastrectomy plus vagotomy. Ghrelin secreted by sources other than stomach is likely to have a function in the long-term regulation of body weight after TG.

NPY Y2 and Y4 receptors selective ligands: promising anti-obesity drugs?

Neuropeptide Y (NPY), a potent orexigen peptide widely produced and distributed in arcuate neurons in the hypothalamus, is a promising candidate for the control of appetitive ingestive behavior. In mammals, the signaling is mediated via at least five different cell surface receptors, denoted as Y(1), Y(2), Y(4), Y(5) and Y(6). Obesity is an important public health problem in the world, particularly in developed societies, and has taken on pandemic proportions. The therapeutics of obesity, including appetite suppressants, has increased 453% over the past decade, although issues concerning safety, efficacy, and little knowledge of the pharmacological activity result in the still modest effects of the anti-obesity drugs presently used. Ligands for Y receptors may be of benefit for the treatment of obesity, and recent findings have indicated a promising role of Y(2) and Y(4) in protecting against diet-induced obesity. This review highlights the supporting evidence therapeutic potential of Y(2) and Y(4) receptors antagonists as additional intervention to treat human obesity.

Neuropeptide y receptor selective ligands in the treatment of obesity.

Obesity is a serious public health problem throughout the world, affecting both developed societies and developing countries. The central nervous system has developed a meticulously interconnected circuitry in order to keep us fed and in an adequate nutritional state. One of these consequences is that an energy-dense environment favors the development of obesity. Neuropeptide Y (NPY) is one of the most abundant and widely distributed peptides in the central nervous system of both rodents and humans and has been implicated in a variety of physiological actions. Within the hypothalamus, NPY plays an essential role in the control of food intake and body weight. Centrally administered NPY causes robust increases in food intake and body weight and, with chronic administration, can eventually produce obesity. NPY activates a population of at least six G protein-coupled Y receptors. NPY analogs exhibit varying degrees of affinity and specificity for these Y receptors. There has been renewed speculation that ligands for Y receptors may be of benefit for the treatment of obesity. This review highlights the therapeutic potential of Y(1), Y(2), Y(4), and Y(5) receptor agonists and antagonists as additional intervention to treat human obesity.