The central role of the non alcoholic fatty liver disease in metabolic syndrome.

Non-alcoholic fatty liver disease (NAFLD) covers a spectrum of liver disease from steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. Most NAFLD patients are hyperinsulinaemic and more insulin resistant compared with nonsteatotic healthy subjects, and there is a near universal association between NAFLD and insulinresistance (IR) irrespective of obesity. The metabolic syndrome (MS) is highly prevalent in the general adult population (approximatively 22%) and it carries an increased cardiovascular morbidity and mortality. Pathophysiologic considerations, clinical associations, and laboratory investigations support that IR and hyperinsulinaemia have a central role in pathogenesis of both MS and NAFLD. The fatty liver is resistant to the action of insulin to suppress hepatic glucose production, which results in hyperglycaemia and, further, in hyperinsulinemia. The MS is associated with maldistribution of body fat, increased free fatty acids (FFAs) and IR, leading to type 2 diabetes, hypertension, dyslipidemia. Visceral fat is an important clinical marker of metabolic cardiovascular risk and a marker of IR in multiple tissues, independent of body mass index (BMI). NAFLD and atherosclerosis share common molecular mediators and NAFLD itself might play an early role in the development and progression of atherosclerosis. These data suggest that NAFLD should be considered part of a multi-organ system derangement in insulin sensitivity, and help explain why NAFLD is so closely linked with diabetes, MS and is an important risk factor for coronary heart disease. NAFLD may be the hepatic manifestation of the MS and raises the possibility that it may play an early role in the etiology of MS.