Role of mitochondria in nonalcoholic fatty liver disease.
Nonalcoholic fatty liver disease (NAFLD) affects about 30% of the general population in the United States and includes a spectrum of disease that includes simple steatosis, non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. Significant insight has been gained into our understanding of the pathogenesis of NALFD; however the key metabolic aberrations underlying lipid accumulation in hepatocytes and the progression of NAFLD remain to be elucidated. Accumulating and emerging evidence indicate that hepatic mitochondria play a critical role in the development and pathogenesis of steatosis and NAFLD. Here, we review studies that document a link between the pathogenesis of NAFLD and hepatic mitochondrial dysfunction with particular focus on new insights into the role of impaired fatty acid oxidation, the transcription factor peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), and sirtuins in development and progression of NAFLD.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Missouri, Columbia, MO 65212, USA. nassirf@health.missouri.edu.
Fatiha
F
Nassir
Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Missouri, Columbia, MO 65212, USA. ibdahj@health.missouri.edu.
Jamal A
JA
Ibdah
D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism*; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D018384:Oxidative Stress; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D056564:Sirtuin 1 / Q000378:metabolism; D056566:Sirtuin 3 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D005227:Fatty Acids; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors; D056564:Sirtuin 1; D056566:Sirtuin 3