Sex Differences in Adipose Tissue Biology and Metabolic Disease

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DESCRIPTION (provided by applicant): This proposal for a Seeding proposal for Collaborative Interdisciplinary Research Program in Diabetes, Endocrinology and Metabolic Diseases will focus on sex differences in obesity and fat distribution and their impact on risk for T2D. Premenopausal women are at lower risk for metabolic disease than post-menopausal women or men. An upper body fat distribution exacerbates risk in both sexes, while lower body fat is protective. We postulate that in addition to effects of biological sex (-1-/- Y chromosomes, sex steroids regulate adipose tissue inflammation and remodeling in a fat depot- and sex- specific fashion. Our team brings together scientists with strong track records in adipose tissue biology (Greenberg, Fried, Smith), sex steroids (Bhasin), clinical investigation (Smith, Bhasin) and epigenetics (Choi). During the next year, we will undertake preliminary studies to demonstrate the feasibility and interdisciplinary S3mergisms afforded by of our multi-institutional collaboration. We will share technologies for physiological measurements of adipose oxygenation and vascularity, LC MS analysis of sex steroids, adipose morphology and inflammation (including FACS analysis), datasets on differences depot-specific gene expression, and methods to analyze metabolic phenotypes. The objective is to gain a multi-level understanding of sex steroid action on adipose tissues of men and women, and the relevance of mouse and cell culture models for translational research. To set the stage for our future collaborations, we plan several hypothesis-generating preliminary projects that address sex differences in adipose tissue vascularization and oxygenation, depot-differences in targets of estrogen action in human adipose tissues, signaling pathways that regulate anti-inflammatory effects of sex steroids in adipose tissue, and epigenetic effects of neonatal androgen. Our goal is to achieve an integrated understanding of sex differences in adipose tissue biology as it relates to metabolic risk, providing a framework for translation into the targeted therapies RELEVANCE (See instmctions): Although percent body fat is higher in women than men, they store more fat in a more 'pear-shaped' pattern (buttocks and thighs) and this is associated with lower risk for developing chronic diseases such as diabetes. The goal of our research is to understand how sex honnones (estrogen and testosterone) affect fat distribution and how fat accumulation in different parts of the body affects risk for disease.