ABSTRACT
Introduction ............................................................................................................ 138 Alcoholic Liver Disease ......................................................................................... 138
Role of Mitochondria in Alcohol Metabolism in the Liver ............................... 138 Mitochondrial Dysfunction Paradigm of ALD ................................................. 140 Reassessment of Mitochondrial Changes in ALD ............................................ 141
Variations in Mitochondrial Changes among Different Alcohol Models ..... 141 Mitochondrial ROS Generation following Alcohol Feeding ........................ 142 Mitochondria as the Final Target of JNK-Induced Apoptosis in ALD ......... 143
Nonalcoholic Fatty Liver Disease .......................................................................... 143 Pathology of NAFLD ........................................................................................ 143 Animal Models for NAFLD and NASH ........................................................... 144 Mitochondrial Alterations Associated with NAFLD and NASH ...................... 145
Mitochondrial Bioenergetic Changes Associated with Steatosis ................. 145 Mitochondria as Sources of ROS in NAFLD ............................................... 146 Mitochondria as the Final Target of JNK-Induced Apoptosis in NAFLD .... 146
Mitochondrial Dysfunction or Mitochondrial Adaptation in ALD and NAFLD? .... 147 Mitochondrial Dynamics and Adaptation ......................................................... 147
Mitochondrial Dysfunction or Mitochondrial Adaptation in ALD .............. 148 Model of Mitochondrial Adaptation in ALD and NAFLD ............................... 149
Summary ................................................................................................................ 150 References .............................................................................................................. 150
Fat accumulation in the liver (steatosis) is associated with alcohol consumption, obesity, and many metabolic disorders [1,2]. Cases of fatty liver have been dramatically increasing in the United States due in part to increasing rates of obesity and metabolic syndromes. Although fat accumulation in the liver is considered somewhat benign, it can dramatically and unpredictably progress to more serious conditions such as steatohepatitis (fatty liver and inammation) and in severe cases, cirrhosis (brosis of liver and extensive hepatocyte death) [1,2]. Liver diseases associated with steatosis are generally divided into two broad categories: alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD). As the name suggests, ALD is associated with chronic alcohol intake, which triggers steatosis. NAFLD, meanwhile, is associated with obesity and metabolic disorders. Although the causes of ALD and NAFLD are different, the two liver pathologies share many biochemical and histological similarities.
