Fat metabolism in human obesity.
Excessive fat turnover and oxidation might cause the insulin resistance of carbohydrate metabolism in obese humans. We studied the response of free fatty acid (FFA) metabolism in lean and obese volunteers to sequential 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 ([1-14C]palmitate), and lipolysis ([2H5]glycerol) were shifted 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. After the overnight fast, FFA turnover per fat mass was decreased in obese subjects (37 +/- 4 vs. 20 +/- 3 mumol.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 leaving 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 mumol.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 mumol.kg FFM-1.min-1, P < 0.01), since FFA oxidation was the same in the two groups throughout the insulin dose-response curve.(ABSTRACT TRUNCATED AT 250 WORDS)
Campbell
P J
PJ
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Carlson
M G
MG
Nurjhan
N
N
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D004951:Esterification; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008066:Lipolysis; D008297:Male; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D009994:Osmolar Concentration; D010084:Oxidation-Reduction
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin