VLDL-triglyceride kinetics during hyperglycemia-hyperinsulinemia: Effects of sex and obesity

We have previously shown that sex and obesity independently affect basal very low density lipoprotein (VLDL)-triglyceride (TG) kinetics. In the present study, we investigated the effect of hyperglycemia-hyperinsulinemia on VLDL-TG kinetics in lean and obese men and women (n = 6 in each group). VLDL-TG kinetics were measured during basal, postabsorptive conditions and during glucose infusion (5.5 mg·kg FFM-^-1·min^-1) by using [²H₅]glycerol bolus injection in conjunction with compartmental modeling analysis. Basal VLDL-TG secretion in plasma was greater in obese than in lean men (7.8 ± 0.6 and 2.9 ± 0.4 μmol·l plasma^-1·min^-1; P < 0.001) but was not different in lean and obese women (5.0 ± 1.1 and 5.9 ± 1.1 μmol·l plasma^-1·min^-1). Glucose infusion decreased the VLDL-TG secretion rate by ∼50% in lean and obese men and in lean women (to 1.5 ± 0.4, 4.0 ± 0.6, and 2.2 ± 0.4 μmol·l plasma^-1·min^-1, respectively; all P < 0.05) but had no effect on the VLDL-TG secretion rate in obese women (4.9 ± 1.0 μmol·l plasma^-1·min^-1). These results demonstrate that both sex and adiposity affect the regulation of VLDL-TG metabolism. Glucose and insulin decrease VLDL-TG production in both lean men and lean women; obesity is associated with resistance to the glucose-and insulin-mediated suppression of VLDL-TG secretion in women, but not in men.