The complex metabolic mechanisms relating obesity to hypertriglyceridemia.

The importance of hypertriglyceridemia as a cardiovascular disease risk factor continues to be a controversial topic,1 and patients with obesity frequently exhibit hypertriglyceridemia. In the Framingham Heart Study, the incidence of coronary heart disease was significantly greater with than without insulin resistance at either the lowest plasma highdensity lipoprotein cholesterol values or the highest triglyceride values.2 The mechanism of hypertriglyceridemia in the setting of obesity has been linked to insulin resistance, wherein an increased flux of adipose tissue–derived free fatty acids (FFAs) gives rise to increased rates of hepatic triglyceride synthesis and secretion of very-low-density lipoprotein (VLDL) triglycerides (Figure).3,4 A recent report has also related increased FFA flux to the secretion of apolipoprotein CIII (apoCIII)-containing VLDL.4 Moreover, there is additional evidence that the hyperinsulinemia that ensues in the setting of insulin resistance is associated with increases in intrahepatic gene expression of genes of triglyceride biosynthesis, eg, sterol regulatory element-binding protein-1C.5 In the presence of increased intrahepatic triglycerides, nonalcoholic fatty liver disease or hypertriglyceridemia often occur, yet not all patients with obesity are insulin resistant.