Molecular Mechanisms of Alcoholic Fatty Liver

• Published in: Alcoholism, clinical and experimental research clinical and experimental research, 2009-02, Vol.33 (2), p.191-205
• Main Authors: Purohit, Vishnudutt, Gao, Bin, Song, Byoung-Joon
• Format: Article
• Language: English
• Subjects: Addictive behaviors; Adipokines; Adult and adolescent clinical studies; Alcohol; Alcoholism; Alcoholism and acute alcohol poisoning; Animals; Biological and medical sciences; Complement C3 - metabolism; Complement C3 - physiology; Cytokines; Fatty Liver; Fatty Liver, Alcoholic - genetics; Fatty Liver, Alcoholic - metabolism; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; NAD - metabolism; NAD - physiology; NADH/NAD; Other diseases. Semiology; Oxidation of Fatty Acids; Oxidative Stress; PPAR alpha - metabolism; PPAR alpha - physiology; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Signaling Pathways; Sterol Regulatory Element Binding Proteins - metabolism; Sterol Regulatory Element Binding Proteins - physiology; Toxicology; Tumor Necrosis Factor-alpha - metabolism; Tumor Necrosis Factor-alpha - physiology
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1111/j.1530-0277.2008.00827.x

Alcoholic fatty liver is a potentially pathologic condition which can progress to steatohepatitis, fibrosis, and cirrhosis if alcohol consumption is continued. Alcohol exposure may induce fatty liver by increasing NADH/NAD+ ratio, increasing sterol regulatory element‐binding protein‐1 (SREBP‐1) activity, decreasing peroxisome proliferator‐activated receptor‐α (PPAR‐α) activity, and increasing complement C3 hepatic levels. Alcohol may increase SREBP‐1 activity by decreasing the activities of AMP‐activated protein kinase and sirtuin‐1. Tumor necrosis factor‐α (TNF‐α) produced in response to alcohol exposure may cause fatty liver by up‐regulating SREBP‐1 activity, whereas betaine and pioglitazone may attenuate fatty liver by down‐regulating SREBP‐1 activity. PPAR‐α agonists have potentials to attenuate alcoholic fatty liver. Adiponectin and interleukin‐6 may attenuate alcoholic fatty liver by up‐regulating PPAR‐α and insulin signaling pathways while down‐regulating SREBP‐1 activity and suppressing TNF‐α production. Recent studies show that paracrine activation of hepatic cannabinoid receptor 1 by hepatic stellate cell‐derived endocannabinoids also contributes to the development of alcoholic fatty liver. Furthermore, oxidative modifications and inactivation of the enzymes involved in the mitochondrial and/or peroxisomal β‐oxidation of fatty acids could contribute to fat accumulation in the liver.