The long term objectives of this proposal are to characterize further the blunted ability of hormones to stimulate lipolysis in adipocytes isolated from older rats and people and to investigate the mechanism for these changes. Our preliminary results have suggested that enhanced effectiveness of adenosine receptors, which inhibit lipolysis, plays a role in diminishing the lipolytic response of adipocytes from older Sprague-Dawley rats. We plan to extend our preliminary results to Sprague-Dawley rats up to 24-months-old. Also Fischer 34 rats which do not become obese with age will be studied at 2, 12 and 24 months. Experiments will be designed to examine the possibility that calorie restriction or exercise retard or prevent the development of the age-related less in catecholamine-induced lipolysis in rat adipocytes. In these studies, lipolysis will be measured in isolated adipocytes and the role of adenosine receptor mediated inhibition of lipolysis determined. To test the relevance of the results of these experiments to man, similar experiments will be conducted in adipocytes removed by fat biopsy from human beings of various ages. The mechanism of the enhanced adenosine effects will be explored by measurements of adenosine receptors, adenosine receptor-mediated inhibition of adenylate cyclase, and quantitation of Ni, the inhibitory regulatory protein. An effort will be made to establish in cell culture preadipocytes derived from epididymal fat pads of various aged rats. These cells could provide the possibility of examining age-related changes in lipolysis in a very controlled setting. It is hoped that the results of the experiments will have some general implications for hormone action in aging.
