My career goal is to be an independent academic research scientist. As a basic science researcher, I am eager to see that my results can be used to help patients. For my research area, I am particularly interested in understanding the molecular mechanisms underlying obesity and diabetes, with a short-term goal of understanding how androgens regulate white adipocyte functions. Under supervision of Dr. Bert O'Malley and Dr. Lawrence Chan, the proposed award will provide sufficient time and support for me to develop skills that can be used for obesity and diabetes research, to garner sufficient data to substantiate R01 funding, and to facilitate my advancement to independent investigator status. Obesity is caused by increased fat cell number and fat cell size, resulting in increased adipose tissue mass. It is likely that manipulation of adipocyte function might be a useful strategy in treating metabolic diseases. Since androgens appear to be important regulators of fat mass and fat distribution in mammals, my short-term goal is to understand how androgens regulate white adipocyte functions. Ultimately, such findings will contribute to better treatment and prevention of obesity and type 2 diabetes mellitus. My current focus is to dissect the molecular mechanisms by which androgens regulate white adipose tissue function. In my specific aim 1, I will determine the function of AR in adipogenic differentiation. I will first prepare 3T3-L1 stable cell lines that express Flag-tagged AR to establish the function of AR in adipogenic differentiation. On the other hand, I will determine adipogenic differentiation of wild type and AR-deficient mouse embryo fibroblast (MEF) cells to establish the function of AR in adipogenic differentiation. In my specific aim 2, I will identify AR target genes in mature white adipocytes by microarray technique. I will prepare primary mature adipocytes from subcutaneous fat pads isolated from wild-type and Tfm male mice and isolate RNA for microarray to identify differentially expressed genes. I will further establish the mechanisms by which AR regulates differentially expressed genes. In my specific aim 3, I will purify and characterize the AR associated coregulator complex in fully differentiated 3T3-L1 cells, and investigate the function of AR coregulators in adipocytes. Obesity is associated with type 2 diabetes, cardiovascular disease, osteoarthritis, hypertension, and cancers. Obesity is caused by dysfunction of fat tissue, which appears to be regulated by androgens. Knowledge in this field may well facilitate the development of adipocyte selective androgen receptor modulators, which may be a useful treatment strategy for obesity-associated metabolic diseases.
