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

Abstract

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 ϳ60 and ϳ70%, 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. intracellular lipolysis; lipid oxidation; postprandial state; lipid metabolism

Time-Dependent Effects of Free Fatty Acids on Glucose Effectiveness in Type 2 Diabetes

“…These findings differ from two reports (27,28) in which nicotinic acid reduced glycerol levels in fasting individuals. However, a recent study (29) using nicotinic acid in the presence of high physiologic insulin was consistent with our findings, since nicotinic acid lowered FFAs but had no effect on plasma glycerol levels. Of note, the former pair of studies were performed under basal fasting conditions, while the latter pair of studies were in the presence of hyperinsulinemia and hyperglycemia, respectively.…”

Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans

“…This difference in extent of EMG activity thus masked any possibility of discerning a correlation between nonshivering thermogenesis and TEE. Change in total heat production was calculated by indirect calorimetry (Vmax 29n; Sensormedics) (29) at room temperature and between times of 180 to 200 minutes and 280 to 300 minutes (i.e., 60 to 80 minutes and 160 to 180 minutes after the beginning of cold exposure). TEE rapidly increased by time 180 to 200 minutes to approximately 79% of that recorded between times 280 and 300 minutes.…”

“…RaNEFA was measured using i.v. administration of [U-13 C]-palmitate during protocol B using the Steele steady-state equation, as previously described (29,35). Tissue oxidative metabolism was determined after i.v.…”

Brothers of women with polycystic ovary syndrome are characterised by impaired glucose tolerance, reduced insulin sensitivity and related metabolic defects

“…At approximately 09:00 hours, a standard OGTT was performed by administering 75 g glucose orally and the AUCs for glucose and insulin response curves were calculated by the trapezoidal rule using absolute values. Finally, participants were instructed to maintain an isocaloric standard diet for 48 h prior to the euglycaemic-hyperinsulinaemic clamp [27].…”

“…An insulin dose of 40 mU m −2 min −1 was used and total-body carbohydrate metabolism (M value, μmol kg −1 min −1 ) was calculated as follows: glucose infusion rate during the last 30 min of the clamp (μmol/min) divided by the participant's weight (kg) [28] [27,30].…”