Effect of insulin infusion on spillover of meal-derived fatty acids

Spillover of chylomicron triglyceride fatty acids directly into the circulation as free fatty acids (FFAs) during lipoprotein lipase hydrolysis may contribute to the elevated total FFAs seen in insulin-resistant states.The objective of the study was to determine whether spillover is regulated by rates of intracellular lipolysis, we studied overweight and obese nondiabetic subjects (n = 7) on two occasions, during infusion of saline and insulin.During insulin infusion (20 mU · m(-2) · min(-1)), plasma glucose was clamped at the concentration achieved during saline infusion. On both study days, subjects sipped 1-2 oz of a liquid mixed meal every 15 min for 6.5 h to achieve steady-state chylomicron and FFA concentrations. Spillover was measured with infusions of [(3)H]triolein and [U-(13)C] oleate.Glucose concentrations were similar during saline compared with insulin (113 ± 2 vs. 113 ± 1 mg/dl, P = NS). Insulin levels during saline and insulin infusion were 18 ± 3 and 44 ± 5 μU/ml, respectively. Glucose infusion rate during insulin infusion was 5.5 ± 1.0 mg · kg fat-free mass(-1) · min(-1). Plasma FFA concentrations were lower during insulin compared with saline (75 ± 8 vs. 124 ± 13 μmol/liter, P = 0.002). Oleate rate of appearance was lower during insulin vs. saline (27 ± 3 vs. 36 ± 5 μmol/min, P = 0.004). Spillover was similar during saline and insulin (26 ± 2 vs. 25 ± 2%, P = 0.60).These results indicate that suppression of intracellular lipolysis with insulin does not reduce lipoprotein lipase-mediated spillover in humans during meal absorption. It is possible that spillover did not decrease because of an impaired or absent antilipolytic effect of increased insulin concentrations in visceral fat.