CONTRIBUTIONS OF DE-NOVO SYNTHESIS OF FATTY-ACIDS TO TOTAL VLDL-TRIGLYCERIDE SECRETION DURING PROLONGED HYPERGLYCEMIA HYPERINSULINEMIA IN NORMAL MAN

Triglycerides (TG) are synthesized in the liver principally from two s ources of fatty acids (FA): FA synthesized de novo in the liver and pr eformed FA, We have measured the rate of secretion of de novo synthesi zed FA and total secretion of FA bound to VLDL-TC in healthy men (n = 5) in the basal state, and after 1 (day 1) and 4 d (day 4) of a hyperc aloric carbohydrate diet (approximate to 2.5 times energy expenditure) that generated a moderate endogenous hyperinsulinemia (plasma insulin approximate to 60 mu U/ml). Prolonged carbohydrate hyperalimentation/ hyperinsulinemia increased plasma VLDL-TG approximate to 10-fold in pa rt due to a 3.4-fold increase in total VLDL-TG secretion rate (basal s tate = 72+/-23, day 4 = 242+/-78 mu mol TG/kg/d). Although the secreti on of de novo synthesized FA increased throughout the study (basal sta te = 1.1+/-0.4, day 1 = 15.9+/-7.9, day 4 = 50.0+/-18.8 mu mol TG/kg/d ), the 2.7-fold increase in secretion rate of preformed FA (basal stat e = 70+/-23, day 4 = 191+/-57 mu mol TG/kg/d) quantitatively contribut ed the most to total VLDL-TG secretion rate. Decreased catabolism of V LDL-TG also contributed to the hypertriglyceridemia as reflected by an approximately fourfold decrease in both fractional turnover rate (bas al state = 9.2+/-3.8, day 1 = 2.1+/-0.2, day 4 = 2.1+/-0.3 pools/d) an d rate of clearance (basal state = 0.35+/-0.08, day 1 = 0.11+/-0.01, d ay 4 = 0.09+/-0.01 liter/kg/d) of VLDL-TG. Thus, the primary differenc e between 1 and 4 d of hyperinsulinemia in conjunction with carbohydra te hyperalimentation is the increase in hepatic secretion of preformed FA into VLDL-TG.