Dyslipidemia in Obesity

Obesity is associated with an increased risk of atherosclerosis and coronary artery disease, in part due to its strong association with atherogenic dyslipidemia. The latter is characterized by elevated plasma triglycerides, low plasma high-density lipoprotein (HDL) cholesterol, and high plasma concentrations of apolipoprotein (apo) B-containing lipoproteins. Dysregulation of lipoprotein metabolism in obese subjects may be due to a combination of overproduction of very-low-density lipoprotein, decreased catabolism of apoB-containing particles, and increased catabolism of HDL particles. These abnormalities may be consequent on a global metabolic effect of insulin resistance and an excess of visceral fat. Lifestyle modifications (dietary restriction and increased physical activity) are first-line therapies to improve lipid abnormalities in obesity. Pharmacological treatments, such as statins, fibrates, ezetimibe, and fish oils, could also be employed alone or in combination with other agents to optimize the benefit of lifestyle modifications on atherogenic dyslipidemia. Kinetic studies show that improvements in lipid and lipoprotein profiles in obesity can be collectively achieved by several mechanisms of action including decreased secretion and increased catabolism of apoB, as well as increased secretion and decreased catabolism of apoA-I. There are several pipeline therapies for correcting atherogenic abnormalities in lipoprotein metabolism. However, their clinical efficacy, safety, and cost-effectiveness remain to be demonstrated.