Please activate JavaScript!
Please install Adobe Flash Player, click here for download

GRK 1482 Jahrbuch 2011-2014

Abstract Before inititation and after termination of a meal, several different hor- mones are secreted by organs like stomach (ghrelin), gut (secretin) or adipose tissue (leptin). Those hormones convey energy-related in- formation to the melanocortin-system in the brain, which is a central metabolic sensor for energy homeostasis. In this study the effect and sensitivity of secretin and other energy- related peripheral hormones on the melanocortin-system will be ana- lyzed and characterized in mouse models. Introduction Energy homeostasis is regulated by metabolic sen- sor regions in the brain. The main centers of this re- gulation are located in areas of the hypothalamus, like the arcuate nucleus (ARC) or in the brainstem, such as the solitary nucleus (NTS). Peripheral hormones, like leptin from white adi- pose tissue, are transported to those nuclei and contribute to the central control of energy balan- ce. Postprandially there is a secretion of anorectic hormones like PYY (peptide YY), GLP-1 or CCK (cholecystokinin) in the periphery. Those hormo- nes activate anorexigenic neuropeptides like POMC (proopiomelanocortins) in the hypothalamus and cause satiety. For the initiation of a meal, there is a secretion of hunger-hormones, such as ghrelin in the stomach that activate orexigenic neurons, like AgRP (agouti- related protein)-/ NPY (neu-ropeptide Y)-neurons in the hypothalamus. Both, the anorexigenic and orexigenic neurons converge on melanocortin- 4-receptor (Mc4r) expressing neurons in the hypo- thalamus [1]. The duodenal peptide-hormone secretin is a no- vel player in the regulation of food intake. Secretin, which has already been found by Bayliss and Star- ling in 1902, is best known to stimulate the secreti- on of bicarbonate from the exocrine pancreas. Next to other metabolic effects, secretin has recently been found to reduce food intake after i.p. injection in fasted mice [2]. They could also show that this effect is very likely to be mediated by the melano- cortin-system. Still precise information, e.g. which melanocortin-receptor subtype is involved, remains to be figured out. Between common mouse models, there are three mouse inbred strains (AKR/J, SWR/J and C57BL6/J) that differ considerably in their suscep- tibility to gain weight by feeding them a high-fat diet. These mouse strains display an ideal model for analyzing adiposity-related effects on meta- bolism. It might be possible, that they also show different sensitivities for the energy homeostasis regulating effect of peripheral hormones in the me- tabolic sensor regions in the brain. This might lead to various susceptibilities for diet-induced obesity. PhD FELLOWS Page 54 | GRK Progress Report 2011-2014 Sarah-Madeleine Gabler (M.Sc.) Molecular Nutritional Medicine PhD 12/2 Regulation of energy intake by secretin and the hypothalamic melanocortin system