Regulation of ghrelin signalling by AMPK

Summary This project will use genetically modified mice to determine whether deletion of AMPK from ghrelin-sensitive cells can suppress appetite during low-calorie feeding and whether specific targeting of ghrelin-AMPK signalling is an effective strategy to prevent rebound weight gain after dieting.

Project Details

Ghrelin is a hormone that is produced by the stomach and acts in the brain to stimulate appetite, food-related reward behaviour and lipid storage in adipose tissue. Importantly, ghrelin is known to mediate the body weight regain that often follows diet-induced weight loss. We have shown that regulation of lipid metabolism in the hypothalamus by the energy sensing enzyme AMP-activated protein kinase (AMPK) is required for increases in appetite in response to low energy conditions, such as fasting or cold exposure. Furthermore, we have evidence that this process is mediated by ghrelin and that disrupting AMPK signalling suppresses ghrelin-induced body weight gain. This project will use genetically modified mice to determine whether deletion of AMPK from ghrelin-sensitive cells can suppress appetite during low-calorie feeding and whether specific targeting of ghrelin-AMPK signalling is an effective strategy to prevent rebound weight gain after dieting. This study will involve comprehensive metabolic analyses in mice including measurements of body composition, energy expenditure, physical activity, metabolic flexibility, food intake behaviour and glucose tolerance. In addition the project will offer training in a range of biochemical and histological techniques, such as analyses of fatty acid synthesis and oxidation, kinase activity, gene expression, immunoblotting, immunohistochemistry and ELISA.