The role of BRCA1 in regulation of lipid metabolism in skeletal muscle

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DESCRIPTION (provided by applicant): Menopause begins in the fifth decade of life and results in decreased circulating estrogens which coincides with increases in visceral fat mass placing women at elevated risk for the developing the metabolic syndrome. With the release of the Women's Health Initiative doctors have to reconsider current options for treating postmenopausal women. It is increasingly important to understand the physiological consequences of the loss of ovarian hormones (i.e. estrogens) on women's health so new interventions can be developed. Our data indicate that ovariectomized animals (OVX) exhibit symptoms of the metabolic syndrome, including increased visceral fat, impaired glucose dynamics and high circulating levels of lipid. We believe these changes in the OVX mice are due to a reduced ability of the skeletal muscle to effectively oxidize lipid, which we hypothesize is mediated in part by the gene breast cancer early onset 1 (BRCA1). This study will delineate the role of BRCA1 in regulating lipid entry into the mitochondria of skeletal muscle and attempt to determine if decreases in BRCA1 expression contribute to increased abdominal obesity in the OVX model.