Abdominal obesity, insulin resistance, metabolic syndrome and cholesterol homeostasis

• Metabolic syndrome is associated with perturbed whole-body cholesterol homeostasis.
• Visceral adiposity influences both cholesterol synthesis and absorption.
• Insulin resistance may also contribute to these metabolic alterations.
• How a perturbed whole-body cholesterol homeostasis affect CHD risk remains unclear.

Reducing low-density lipoprotein-cholesterol (LDL-C) concentrations is the primary therapeutic target for the prevention of coronary heart disease (CHD). However, several other cardiometabolic risk factors such as the ones associated with metabolic syndrome also predict an increased risk of CHD, often in the absence of elevated LDL-C concentrations. Evidence is now emerging to suggest that whole-body cholesterol homeostasis, which is perturbed in metabolic syndrome, may be related to the risk of CHD, independent of concurrent variations in LDL-C. Studies have suggested that metabolic syndrome is associated with an increased endogenous synthesis of cholesterol and reduced intestinal cholesterol absorption. Both abdominal obesity and insulin resistance have been associated with the subtle disruptions in cholesterol homeostasis seen in metabolic syndrome. This review examines how abdominal obesity and insulin resistance may each contribute to perturbations in whole-body cholesterol homeostasis in the context of metabolic syndrome.