A. Aarsland et al., CONTRIBUTIONS OF DE-NOVO SYNTHESIS OF FATTY-ACIDS TO TOTAL VLDL-TRIGLYCERIDE SECRETION DURING PROLONGED HYPERGLYCEMIA HYPERINSULINEMIA IN NORMAL MAN, The Journal of clinical investigation, 98(9), 1996, pp. 2008-2017
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.