Interaction between free fatty acids and insulin in the acute control of very low density lipoprotein production in humans.

Abstract

Changes in VLDL triglyceride and VLDL apo B production were determined semiquantitatively in healthy young men by examining the effect of altering plasma insulin and/or FFA levels on the change in the slopes of the specific activity of VLDL [3H]triglyceride glycerol or the "'I-VLDL apo B versus time curves.In one study (n = 8) insulin was infused for 5 h using the euglycemic hyperinsulinemic clamp technique. Plasma FFA levels declined by 80% (0.52±0.01 to 0.11±0.02 mmol/liter), VLDL triglyceride production decreased by 66.7±4.2% (P = 0.0001) and VLDL apo B production decreased by 51.7±10.6% (P = 0.003). In a second study (n = 8) heparin and Intralipid (Baxter Corp., Toronto, Canada) were infused with insulin to prevent the insulin-mediated fall in plasma FFA levels. Plasma FFA increased approximately twofold (0.43±0.05 to 0.82 + 0.13 mmol/liter), VLDL triglyceride production decreased to a lesser extent than with insulin alone (P = 0.006) (-31.8±9.5%, decrease from baseline P = 0.03) and VLDL apo B production did not decrease significantly ( -6.3±13.6%, P = NS). In a third study (n = 8) when heparin and Intralipid were infused without insulin, FFA levels rose approximately twofold (0.53±0.04 to 0.85±0.1 mmol/liter), VLDL triglyceride production increased by 180.1±45.7% (P = 0.008) and VLDL apo B production increased by 94.2+28.7% (P = 0.05). We confirm our previous observation that acute hyperinsulinemia suppresses VLDL triglyceride and VLDL apo B production in healthy humans. In addition, we have demonstrated that elevation of plasma FFA levels acutely stimulates VLDL production in vivo in healthy young males. Elevating plasma FFA during hyperinsulinemia attenuates but does not completely abolish the suppressive effect of insulin on VLDL production, at least with respect to VLDL triglycerides. Therefore, in normal individuals the acute inhibition This work was presented in part at

Defective regulation of triglyceride metabolism by insulin in the liver in NIDDM

“…We speculate that the variability of available lipid pool in the liver may influence VLDL apo B production and insulin action. The in vivo findings of the present and previous [7] studies concur with the suggestion from cell culture work that there may be two separate mechanisms by which insulin regulates plasma triglyceride metabolism. VLDL secretion in hepatocytes is known to be stimulated by the amount of fatty acid delivered to cells and also to be inhibited by insulin in a manner which increases cellular triglyceride deposits [31][32][33] and possibly promotes intracellular apo B degradation.…”

“…A majority of studies indicate that the elevation of plasma triglycerides in NIDDM result from an overproduction of VLDL triglyceride [2,3] and apo B [4,5] but it is unclear and a matter of controversy whether the increased production of VLDL particles is driven by a direct effect of hyperinsulinaemia or is a consequence of defective suppression of VLDL production by insulin [1]. In healthy subjects acute insulin administration suppresses VLDL apo B production [6][7][8]. Data on the suppression of VLDL production by insulin in insulin resistant states are controversial.…”

Normal metabolism of apolipoprotein B100-containing lipoproteins despite qualitative abnormalities in type 1 diabetic men

“…This hypothesis is supported by the results of in vitro studies demonstrating that hepatocytes are able to secrete apoB-containing lipoproteins with variable triglyceride contents, depending on the intracellular availability of triglycerides [16]. Moreover, in humans, we know from simultaneous kinetic studies of VLDL triglycerides and apoB100 that variations in VLDL triglycerides and apoB production rates are not directly related [20,21]. The reasons for the decreased production rate of VLDL triglycerides in type 1 diabetic patients treated with subcutaneous insulin are not fully understood.…”

Role of insulin in hepatic fatty acid partitioning: emerging concepts

“…-associated TAG is decreased [98]. Although a large proportion of this effect can be attributed to the decrease in circulating NEFA concentrations due to the anti-lipolytic action of insulin, even when the concentration of NEFA was kept high, insulin still gave a decrease in hepatic VLDL secretion rate of about 30 % [98]. In humans, the concentrations of both apoB %) (from the gut) and of apoB "!!…”