GRK 1208: Hormonal adaptation to metabolic changes as result of selection and excessive energy supply in the Berlin fat mouse line

As a novel model for polygenic obesity, we use the unique high fatness-selected and inbred Berlin Fat Mouse (BFM) line. The initial fat percentage of about 25% under standard diet is additionally increased at high fat diet. To elucidate the mechanisms of hormonal adaptation to the selection response and to dietary stimuli for obesity, in a first step, selected BFM and unselected control mice will be systematically analyzed regarding endocrine profiles and metabolites known to effect obesity and body composition in dependency of age and diet. The adipose tissue acts as an endocrine organ with effect on energy homeostasis. Therefore, specific hormonal regulatory circuits of adipose tissue (including leptin, adiponectin, resistin) will be analyzed in response to selection for obesity and dietary stimuli. The joined analysis of individual data for body composition, endocrine profiles, metabolites and fat tissue specific gene expression will provide insight into endocrine mechanisms of adaptation to different levels of energy homeostasis. In a second step, hormone concentrations, which are significantly different between selected and unselected mice, will be measured in animals of a segregating pedigree and used in linkage analyses to identify genetic factors that influence the hormonal network as result of selection for obesity. In the segregating pedigree, we expect obese phenotypes with different hormonal adaptation to metabolic changes at low and high energy diet.