On the suppression of plasma nonesterified fatty acids by insulin during enhanced intravascular lipolysis in humans

During the fasting state, insulin reduces nonesterified fatty acid (NEFA) appearance in the systemic circulation mostly by suppressing intracellular lipolysis in the adipose tissue. In the postprandial state, insulin may also control NEFA appearance through enhanced trapping into the adipose tissue of NEFA derived from intravascular triglyceride lipolysis. To determine the contribution of suppression of intracellular lipolysis in the modulation of plasma NEFA metabolism by insulin during enhanced intravascular triglyceride lipolysis, 10 healthy nonobese subjects underwent pancreatic clamps at fasting vs. high physiological insulin level with intravenous infusion of heparin plus Intralipid. Nicotinic acid was administered orally during the last 2 h of each 4-h clamp to inhibit intracellular lipolysis and assess insulin's effect on plasma NEFA metabolism independently of its effect on intracellular lipolysis. Stable isotope tracers of palmitate, acetate, and glycerol were used to assess plasma NEFA metabolism and total triglyceride lipolysis in each participant. The glycerol appearance rate was similar during fasting vs. high insulin level, but plasma NEFA levels were significantly lowered by insulin. Nicotinic acid significantly blunted the insulin-mediated suppression of plasma palmitate appearance and oxidation rates by approximately 60 and approximately 70%, respectively. In contrast, nicotinic acid did not affect the marked stimulation of palmitate clearance by insulin. Thus most of the insulin-mediated reduction of plasma NEFA appearance and oxidation can be explained by suppression of intracellular lipolysis during enhanced intravascular triglyceride lipolysis in healthy humans. Our results also suggest that insulin may affect plasma NEFA clearance independently of the suppression of intracellular lipolysis.