The Contribution of Splanchnic Fat to VLDL Triglyceride Is Greater in Insulin-Resistant Than Insulin-Sensitive Men and Women

Abstract

OBJECTIVE—We aimed to determine differences in the postprandial contributions of different fatty acid sources to VLDL triglycerides (TGs) in healthy men and women with varying degrees of insulin resistance. RESEARCH DESIGN AND METHODS—Insulin-resistant (n = 11) and insulin-sensitive (n = 11) men and women (n = 6) were given an intravenous infusion of [2H2]palmitic acid to investigate systemic nonesterified fatty acid (NEFA) incorporation into VLDL TGs. Participants were also fed a mixed meal containing [U-13C]palmitic acid to investigate the contribution of dietary fatty acids to VLDL TG production. Blood samples were taken over the following 6 h. Separation of VLDL was performed by density gradient ultracentrifugation and immunoaffinity techniques specific to apolipoprotein B-100. RESULTS—Insulin-resistant and insulin-sensitive men had similar postprandial chylomicron and chylomicron remnant TG concentrations, but insulin-resistant men had higher postprandial VLDL TG concentrations (median [range]; area under the curve 485 μmol/l [123–992] vs. 287 μmol/l [162–510]; P < 0.05). At 360 min, most of the difference in VLDL TGs was accounted for by an additional contribution from splanchnic fat (means ± SE; 331 ± 76 μmol/l vs. 89 ± 25 μmol/l; P < 0.01). The contribution of fatty acids from endogenous systemic NEFAs was similar across the groups, as were dietary fatty acids. There was no difference in the VLDL TG concentration or the contribution of different fatty acid sources between insulin-sensitive men and women. CONCLUSIONS—In the postprandial period, the only sources of fatty acids for VLDL TG production to differ in the insulin-resistant compared with the insulin-sensitive men are those derived from splanchnic sources.