Pharmacologic strategies for maintance of weight loss in diet induced obese mice

• Applicant: Dr. Petra Wiedmer, Ph.D.
• Subject Area: Pediatric and Adolescent Medicine ; Endocrinology, Diabetology, Metabolism ; Nutritional Sciences
• Term: from 2009 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 101434729

In this project we will utilize the model of the diet-induced obese (DIO) mouse and the MC4 receptor mutant mouse (the latter in cooperation with TP5) for studying hormonal replacement effects during diet-induced weight loss and maintenance of the reduced weight. We aim at identifying an appropriate combined replacement therapy of leptin, a ghrelin receptor antagonist and thyroid hormone (the latter in collaboration with project TP3) in the state of reduced weight that will prevent or decelerate rapid weight regain following a period of restricted feeding. We will first establish a profile of changes in leptin, ghrelin and thyroid hormones as well as energy metabolism during weight loss and regain This will be achieved by quantification of specific active hormone plasma levels and parameters of energy balance (e.g. food intake, metabolic rate, respiratory quotient, locomotor activity) during several stages of weight loss, weight maintenance and weight regain. Constitutively, we will develop and test combination treatments of leptin with either ghrelin receptor antagonist and/or thyroid hormones (the latter in cooperation with project TP3) in order to test the hypothesis that successful adjustment of a specific hormone deficiency pattern associated with reduced body weight will improve the ability to maintain a lower body weight.

• DFG Programme: Clinical Research Units
• Subproject of: KFO 218: Hormonal Regulation of Body Weight Maintenance