Role of ghrelin in neuroadaption of appetite-regulating brain networks in diet-induced obesity

• Applicant: Dr. Heike Vogel
• Subject Area: Nutritional Sciences
• Term: from 2012 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 223283435

Obesity continues to present a serious medical disease with adverse health consequences e.g. diabetes, cardiovascular disease, and increased cancer risk. Currently, the only effective therapy involves surgical bypass of the stomach (gastric bypass) for which weight loss appears independent of the loss of container function of the stomach. Patients that have undergone gastric bypass completely change their food preference, selecting healthier foods. They also have altered levels of appetite-regulating gut hormones and their brains respond differently to environmental food cues, especially brain areas involved in the food reward mechanism.One of these gut-brain signals, ghrelin, the only known circulating orexigenic hormone whose secretion appears to be suppressed after gastric bypass, targets brain areas involved in reward (e.g. ventral tegmental area, VTA) and stimulates food reward behavior in rodents. Given that the majority of obese individuals show enhanced food reward, together with the observation that ghrelin enhances food reward behavior, it seems possible that ghrelin has a critical role in enhancing food reward/ motivation during the development of obesity.The aim of this study is to test the hypothesis that changes in the ghrelin sensitivity are responsible for neural adaptions that occurs after weight gain and subsequent weight loss induced by food restriction or gastric bypass (RYGB). In the first instance, ghrelin sensitivity will be tested in rodent models of diet-induced obesity by measuring food intake and food reward behavior. Secondly, it will be determined whether ghrelin axis reawakens after food restriction in diet-induced obese mice and how gastric bypass modulates ghrelin sensitivity.

• DFG Programme: Research Fellowships
• International Connection: Sweden
• Host: Professorin Dr. Suzanne L. Dickson