Hepatic lipid metabolism and non-alcoholic fatty liver disease.
Non-alcoholic fatty liver disease (NAFLD) is an increasingly recognized pathology with a high prevalence and a possible evolution to its inflammatory counterpart (non-alcoholic steatohepatitis, or NASH). The pathophysiology of NAFLD and NASH has many links with the metabolic syndrome, sharing a causative factor in insulin resistance. According to a two-hit hypothesis, increased intrahepatic triglyceride accumulation (due to increased synthesis, decreased export, or both) is followed by a second step (or "hit"), which may lead to NASH. The latter likely involves oxidative stress, cytochrome P450 activation, lipid peroxidation, increased inflammatory cytokine production, activation of hepatic stellate cells and apoptosis. However, both "hits" may be caused by the same factors. The aim of this article is to overview the biochemical steps of fat regulation in the liver and the alterations occurring in the pathogenesis of NAFLD and NASH.
Department of Clinical and Experimental Medicine, Chair of Metabolism, University of Padua, Italy. paolo.tessari@unipd.it
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Tiengo
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D054392:Adipokines / Q000378:metabolism; D000818:Animals; D004032:Diet / Q000009:adverse effects; D005227:Fatty Acids / Q000378:metabolism; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D050356:Lipid Metabolism; D050155:Lipogenesis; D008066:Lipolysis; D008074:Lipoproteins / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D015398:Signal Transduction
D054392:Adipokines; D005227:Fatty Acids; D008074:Lipoproteins; D055372:AMP-Activated Protein Kinases