Genetics of the metabolic syndrome and implicationsfor therapy

摘要

Insulin resistance (IR) is a key featuie of several major risk factors for coronary heart disease, including type 2 diabetes, essential hypertension, combined hyperlipidaemia and obesity.These coronary risk factors have been brought together under the term "Metabolic Syndrome", Despite their high prevalence in Western populations, the molecular basis of these risk factors, and their pathogenic relationship to insulin resistance, remain poorly understood.We studied the genetics of insulin resistance in a rodent model of cardiovascular disease, the spontaneously hypertensive rat (SHR) and identified a defective SHR gene, Cd36 or fatty acid translocase, which causes defects in insulin action and fatty acid metabolism in this rat model Cd36 is a transmembrane transporter of long-chain fatty acids and a receptor for oxidised, low-density lipoproteins and has been proposed to play a key part in foam cell formation Cd36 is induced by peroxisome proliferator-activated receptor (gamma) (PPAR(gamma)), the target of the thiazolidinedione insulin-sensitising drugs.Deficiency of Cd36 is associated with reduced action of thiazolidinediones and marked protection against atherosclerosis Elucidation of the mechanisms through which Cd36 influences insulin action and atherogenesis may lead to new insights into the pathogenesis of these common causes of cardiovascular disease and, ultimately, to new therapeutic approaches for their management.? 2003 Elsevier B.V All rights reserved.