FAT-METABOLISM IN HUMAN OBESITY

Excessive fat turnover and oxidation might cause the insulin resistanc e of carbohydrate metabolism in obese humans. We studied the response of free fatty acid (FFA) metabolism in lean and obese volunteers to se quential insulin infusions of 4, 8, 25, and 400 mU.m(-2).min(-1). The insulin dose-response curves for suppression of FFA concentration, FFA turnover ([1-C-14]palmitate), and lipolysis ([H-2(5)]glycerol) were s hifted to the right in the obese subjects (insulin concentrations that produced a half-maximal response, lean vs. obese: 103+/-21 vs. 273+/- 41, 96+/-11 vs. 264+/-44, and 101+/-23 vs. 266+/-44 pM, all P < 0.05), consistent with insulin resistance of FFA metabolism in obesity. Afte r the overnight fast, FFA turnover per fat mass was decreased in obese subjects (37+/-4 vs. 20+/-3 mu mol.kg fat mass(-1).min(-1), P < 0.01) as the result of suppression of lipolysis by the hyperinsulinemia of obesity and an increased fractional reesterification of FFA before lea ving the adipocyte (primary FFA reesterification; 0.14+/-0.03 vs. 0.35 +/-0.06, P < 0.05). Nevertheless, FFA turnover per fat-free mass (FFM) was also greater in the obese volunteers (8.5+/-0.7 vs. 11.0+/-1.0 mu mol.kg FFM(-1).min(-1), P < 0.05) but only as the result of increased reesterification of intravascular FFA (secondary reesterification; 1. 8+/-0.5 vs. 4.8+/-1.1 mu mol.kg FFM(-1).min(-1), P < 0.01), since FFA oxidation was the same in the two groups throughout the insulin dose-r esponse curve. In conclusion, FFA metabolism is resistant to insulin i n obesity. However, the hyperinsulinemia of obesity and increased frac tional primary FFA reesterification reduce FFA turnover per fat mass i n obese humans. FFA oxidation is not increased in obesity and therefor e is not the cause of the insulin resistance of carbohydrate metabolis m.