Metabolic patterns and insulin responsiveness of enlarging fat cells

The rate and pattern of glucose metabolism, basal lipolysis, and intracellular concentration of free fatty acids were determined in isolated epididymal fat cell preparations (mean volume 30-800 pl) from rats on the basis of fat cell number and in relation to the cell volume. The effects of increasing glucose concentrations in the medium and of insulin on the cellular metabolic activities were compared. Expanding fat cell volume correlated positively and significantly (P < 0.001) with the synthesis of glyceride glycerol from glucose (correlation coefficient, r = 0.919), with rates of basal lipolysis (r = 0.663), and with intracellular free fatty acid accumulation (r = 0.796); it correlated negatively and significantly with glucose conversion to glyceride fatty acids (r = -0.814, P < 0.01). The differences in patterns of glucose metabolism and basal lipolysis between small (<100 pl) and large (>400 pl) fat cells were not modified by insulin or by increments in glucose concentration. The results indicate that the reduced capacity of the large fat cells to respond to insulin cannot be attributed solely to a limited capacity of the cells to take up and metabolize increasing amounts of glucose. The acquired unresponsiveness of the large cells to insulin may result from an alteration in the mechanism of action of insulin and may be related to an intracellular metabolic derangement with increased basal lipolysis, free fatty acid accumulation, and accelerated glyceride synthesis resulting from the accumulation of triglyceride.