Studies in animal models of aging have suggested that there is a reduced potenfial for adipocyte maturation during the aging process. This could result in a defective capacity for storage of excess energy during overfeeding, and adipose fissue dysfunction. The resulfing abnormalifies in systemic lipid and glucose metabolism (including insulin resistance) are known contributors to risk for cardiovascular disease, a major cause of disability in the elderiy. We have recently found that when compared to Caucasian controls matched for age, gender and body composifion, young lean Asian Indians have much larger adipocytes and lower indices of new adipocyte formafion, which are associated with a significant reducfion in insulin sensifivity. Our hypothesis is that in older adults a reduced ability to form new adipocytes (whether through lack of proliferation or maturation arrest), in combinafion with adipocyte lepfin resistance, induces adipose fissue dysfuncfion and insulin resistance.
The specific aims that we will test are the following: 1. To determine in subcutaneous abdominal fat if there are age-related differences in the size of the adipocytes, expression of genes involved in new adipocyte formafion (such as pref-1, INSIG-1, PPARgamma), and leptin sensifivity (lepfin receptor, S0CS3, PTP1B, AMPK phosphorylafion). 2. To determine if there are age-related differences in adipose tissue triglycerides kinetics (triglyceride synthesis, net lipolysis, glyceroneogenesis) and adipocyte proliferafion using long-term ^H20 labeling. We will study non-diabefic young and older volunteers matched for gender, body fat content, and fat distribution. The results of this study will provide the necessary preliminary information to apply for larger grants to evaluate the role of adipose fissue dysfuncfion in the development of metabolic abnormalifies associated with aging.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Center Core Grants (P30)
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Special Emphasis Panel (ZAG1-ZIJ-8)
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University of Texas Medical Br Galveston
United States
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