The role of adipose tissue estrogen receptors during body weight loss and the maintenance of reduced weight

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Estrogen receptor (ER) α- and β have been identified as important regulators of body weight. The underlying mechanisms of this regulation remain largely unclear, but point towards major changes of regulatory pathways in adipose tissue metabolism (lipogenesis/lipolysis). In addition, attenuated ERα/β activation during weight reduction may suggest that the preservation of this activity during the weight maintenance phase may be a promising approach to prevent weight regain. A therapeutic ER-based intervention requires a comprehensive knowledge of isoform- and tissue-specific ER-function during the different phases of weight reduction – maintenance – regain. Given the importance of adipose tissue metabolism in ER-mediated modulation of body weight, the present project aims for the characterization of adipose tissue ERα- and ERβ- signaling during the maintenance of reduced body weight after weight reduction and during the weight regain period. For this purpose, adipocyte-specific ERα- and ERβ - deficient mice will be metabolically phenotyped. ER signaling will be comprehensively studied ex-vivo using established protocols for molecular tissue analysis such as EMSA and ChIP, which will be complemented by in-vitro studies in adipocytes. To study the clinical relevance of our hypothesis, ER-signaling will be studied in adipose tissue biopsy samples and monocytes from the Z project of the CRG. In summary, the aim of the present project is the characterization of ERα-/ ERβ-signaling during body weight reduction – maintenance - regain, and to establish ERs as therapeutic targets to maintain long-term weight reduction.