Abstracts of the 5th International Conference of the Society for Heart and Vascular Metabolism

Abstract

Consuming diets rich in fatty acids leading to excessive weight gain has been identified as a major contributor to the pathogenesis of Type 2 Diabetes (T2D), a known risk factor for cardiovascular disease. Associated with diet-induced obesity (DIO) are elevated levels of plasma fatty acids (FA) and lipoprotein associated triglycerides (TG). Since the levels of plasma FA and lipoprotein associated TG are primarily controlled by the liver, it is likely that aberrant hepatic FA uptake and handling contributes to the dyslipidemia that precedes development of T2D. Indeed, we have shown that mRNA and protein expression of the FA transport protein, CD36, which is normally expressed at low levels in the mouse liver, is significantly elevated during DIO and is correlated with increased hepatic TG storage and TG secretion as very low-density lipoproteins (VLDL). In vivo gene delivery of a recombinant adenovirus harboring CD36 cDNA (Ad.CD36) into lean mice showed a significant increase in hepatic FA uptake in vivo and an accumulation in hepatic TG storage and VLDL-TG secretion compared to Ad.Null-injected mice, demonstrating that increased CD36 expression alone is sufficient to recapitulate the alterations in liver lipid storage and VLDL-TG secretion observed in DIO. Together these data show that increased hepatic CD36 expression may play a causative role in the dyslipidemia associated with DIO and further suggests that inhibition of hepatic CD36 may prove to be beneficial for the prevention of insulin resistance and the eventual development of T2D.