Severe obesity in man is a major risk factor for disease that also imposes great physical and psychological burdens on its victims. They, in turn, make great demands on the nation's health care delivery system. Dieting rarely helps any of these people. Their overly enlarged fat cells can be reduced to normal, but usually only by means of risky gastric or intestinal surgery. Elimination of the excessive numbers of fat cells found in the severely obese is as yet impossible. Thus, knowledge of the source of excess fat cells is essential. To this end, we developed and examined animal models in which adipocyte hyperplasia is either rampant or restrained depending upon the diet, the season or the anatomical locus of the tissue being studied. We also raised mouse, anti-rat monoclonal antibodies that we have begun to use in identifying different types of cells in rat adipose tissue. We propose to isolate and study the adipocyte precursors of some of these models in cell culture and with the adi of the antibodies. We also propose to study circulating factors that may contribute to the control of adipocyte hyperplasia in vivo. We propose to: 1. Characterize the different adipose tissue cell populations and subpopulations distinguished by our monoclonal antibodies and determine the specficities of the different antibodies. 2. Use the antibodies and combinations of plating, harvesting, precipitation and electronic cell sorting techniques to create nonclonal primary cell cultures in which virtually all cells are adipose precursors that have not yet committed to differentiate. 3. Establish whether circulating factors in animals showing widely disparate degrees of adipocyte hyperplasia cause similarly disparate proliferation or differentiation of pre-adipocytes in culture.
