Determinants of VLDL-triglycerides production.
Nielsen S., Karpe F.
PURPOSE OF REVIEW: Plasma free fatty acids (FFA) are major substrates for hepatic VLDL-triglycerides (VLDL-TG) production. In addition, it is a common belief that VLDL-TG production is a substrate driven process primarily determined by systemic FFA delivery. This review summarizes recent research of our understanding of the regulation of VLDL-TG production. RECENT FINDINGS: Recent studies have shown that increasing FFA flux is not inevitably associated with increased VLDL-TG production. Exercise induced increase in FFA flux resulting in unchanged VLDL-TG production in lean patients as well as in obese patients with increased hepatic fat despite exercise reduced hepatic fat content. With respect to the other inseparable conditions of insulin resistance and hyperinsulinemia, recent studies demonstrate that increased hepatic VLDL-TG production precedes the insulin resistance-associated impairment of the regulation of hepatic glucose production, whereas isolated chronic hyperinsulinemia (insulinoma) was not associated with increased VLDL-TG production. Insulin has been shown to have acute potent temporary suppressing effect on VLDL-TG production and new data demonstrates that increased glucagon reduces VLDL-TG production. Finally, recent studies indicate that sex hormones, oestrogen and testosterone, have no or very modest impact on VLDL-TG production. SUMMARY: Regulation of hepatic VLDL-TG production involves interplay between systemic FFA delivery, hormonal, and nutritional factors that act in concert with hepatic fatty acid handling to regulate short-term and long-term VLDL-TG production. The results of recent studies underscore that our current understanding of these relationships is complex and needs further research.