White adipose tissue plays an essential role in regulating energy balance through its metabolic and endocrine activities. Adipose tissue is a key regulator of insulin sensitivity, and several lines of evidence indicate that the current epidemic of diabetes stems from the adverse impact of obesity on the function of insulin-sensitive tissues. Significantly, pharmacological agents that effectively treat type 2 diabetes in humans and rodent models target receptors that are enriched in adipose tissue, where receptor activation produces pronounced tissue remodeling. While much has been learned about adipocyte differentiation from cell culture models, analysis of cell dynamics, developmental plasticity and therapeutic tissue remodeling in vivo has not been undertaken owing to lack of appropriate animal models. Therefore, our Specific Aims are: 1) To create a transgenic mouse model for evaluating the turnover and developmental potential of mature adipocytes in vivo. 2) To examine adipose tissue cellular dynamics during therapeutic remodeling induced by agonist activation of beta3-adrenergic receptors and PPAR-gamma.
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