Non alcoholic fatty liver disease and metabolic syndrome

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a clinicopathologic entity increasingly recognized as a major health burden in developed countries. It includes a spectrum of liver damage ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), advanced fibrosis, and rarely, progression to cirrhosis. Recent studies emphasize the role of insulin resistance, oxidative stress and subsequent lipid peroxidation, proinflammatory cytokines, adipokines and mitochondrial dysfunction in the development and progression of NAFLD. Furthermore, accumulating evidence supports an association between NAFLD and metabolic syndrome. Although the data are mainly epidemiological, the pathogenesis of NAFLD and metabolic syndrome seems to have common pathophysiological mechanisms, with focus on insulin resistance as a key factor. This review summarizes the current knowledge on the epidemiology, pathophysiology and diagnosis of both NAFLD and metabolic syndrome and the findings that strongly support the association of nonalcoholic fatty liver disease as a possible component in the cluster of metabolic syndrome.

Keywords: metabolic syndrome; non alcoholic fatty liver disease; non alcoholic steatohepatitis.

Figure 1:. Development of nonalcoholic hepatic steatosis. In adipose tissue, insulin resistance decreases the inhibitory action of insulin on hormone sensitive lipase (HSL), thus enhancing triglyceride (TG) lipolysis and free fatty acid (FFA) release. The results are increased circulating levels of FFAs, which are then taken up by the liver. Dietary fatty acids enter the liver through spillover into the plasma NEFA pool and through the uptake of intestinally derived chylomicron remnants. In hepatocytes hyperinsulinemia increases the 'de novo' synthesis of fatty acids. Hepatic TG synthesis is driven by the increased hepatocyte FFA content and favoured by insulin-mediated upregulation of lipogenic enzymes, such as peroxisome proliferator-activated receptor gamma (PPAR-γ) and sterol regulatory element binding protein 1 (SREBP-1). The large pool of FFAs activates mitochondrial fatty acid β-oxidation by activation of PPAR-α and enchanced CPT-I. Meanwhile, TG export via very-low-density lipoproteins (VLDL) may be inhibited by decreased synthesis of apolipoprotein B (apo B) or reduced incorporation of TG with apo B by microsomal triglyceride transfer protein (MTP). (abbrevations: HSL: hormone-sensitive lipase, TG: triglyceride, FFA: free fatty acid, PPAR-: peroxisome proliferator-activated receptor gamma, SREBP-1: sterol regulatory element binding protein 1, PPAR-α: peroxisome proliferator-activated receptor a, CPT-I: carnitine palmitoyltransferase I, VLDL: very-low-density lipoproteins, apo B: apolipoprotein B, MTP: microsomal triglyceride transfer protein).