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World J Gastroenterol. Oct 7, 2007; 13(37): 4974-4978
Published online Oct 7, 2007. doi: 10.3748/wjg.v13.i37.4974
Alcohol-induced steatosis in liver cells
Terrence M Donohue Jr
Terrence M Donohue Jr, Liver Study Unit, The Omaha Veterans Affairs Medical Center, the Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68105, United States
Author contributions: All authors contributed equally to the work.
Supported by New Research Grant from the University of Nebraska Medical Center, the NIAAA, and Medical Research Funds from the Department of Veterans Affairs, United States
Correspondence to: Terrence M Donohue Jr, PhD, Liver Study Unit, Research Service (151), VA Medical Center, 4101 Woolworth Ave, Omaha, NE 68105, United States. tdonohue@unmc.edu
Telephone: +1-402-3468800- 93556 Fax: +1-402-4490604
Received: June 30, 2007
Revised: July 24, 2007
Accepted: July 26, 2007
Published online: October 7, 2007
Abstract

Alcohol-induced fatty liver (steatosis) was believed to result from excessive generation of reducing equivalents from ethanol metabolism, thereby enhancing fat accumulation. Recent findings have revealed a more complex picture in which ethanol oxidation is still required, but specific transcription as well as humoral factors also have important roles. Transcription factors involved include the sterol regulatory element binding protein 1 (SREBP-1) which is activated to induce genes that regulate lipid biosynthesis. Conversely, ethanol consumption causes a general down-regulation of lipid (fatty acid) oxidation, a reflection of inactivation of the peroxisome proliferator-activated receptor-alpha (PPAR-α) that regulates genes involved in fatty acid oxidation. A third transcription factor is the early growth response-1 (Egr-1), which is strongly induced prior to the onset of steatosis. The activities of all these factors are governed by that of the principal regulatory enzyme, AMP kinase. Important humoral factors, including adiponectin, and tumor necrosis factor-α (TNF-α), also regulate alcohol-induced steatosis. Their levels are affected by alcohol consumption and by each other. This review will summarize the actions of these proteins in ethanol-elicited fatty liver. Because steatosis is now regarded as a significant risk factor for advanced liver pathology, an understanding of the molecular mechanisms in its etiology is essential for development of effective therapies.

Keywords: Ethanol metabolism; Fatty liver; Sterol regulatory element binding protein; Peroxisome proliferator activated receptor; Early growth response-1; Fatty acid toxicity; Triglycerides; Acetaldehyde; Reactive oxygen species