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 high-density 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.Figure. Insulin resistance is associated with an expanded adipose tissue mass. In this setting, many of the metabolic effects of insulin are reduced, including increases in basal lipolysis and less suppression of lipolysis by feeding and insulin. In addition, there is a reduction in the intrahepatic effects of insulin action that relate to apolipoprotein metabolism. Under physiological conditions, insulin suppresses apolipoprotein C-III (apo C-III) gene transcription and increases apolipoprotein B-100 (apo B-100) degradation, whereas in insulin-resistant states, both effects of insulin are reduced. …