ArticleObesity and alcoholic liver disease
Introduction
Alcohol-induced liver disease remains one of the most common and deadly causes of chronic liver disease (Sussman et al., 2002). Given that alcohol is the most commonly abused substance in the United States (Szabo, 2003), it is fortunate that serious liver disease does not develop in most individuals who consume alcohol habitually (Lelbach, 1976, Morgan, 1994, Pequignot et al., 1978). However, results of several population-based studies raise concern that both the prevalence and the severity of alcohol-induced liver disease may be rising in conjunction with the obesity epidemic. Multivariate regression analysis consistently identifies obesity as an independent risk factor for alcohol-induced liver damage. Indeed, obesity seems to increase all stages of alcoholinduced liver disease, including alcoholic fatty liver, alcoholic steatohepatitis, and alcoholic cirrhosis (Bellentani et al., 2000, Naveau et al., 1997, Raynard et al., 2002).
Section snippets
Fat physiology
The liver and adipose tissue interact to regulate fat homeostasis. Adipose tissue is both a source of fatty acids that are delivered to the liver and a storage depot for triglycerides that are produced by liver and released into the bloodstream. During the past several years, it has become apparent that fat also plays a very active role in regulating both intermediary metabolism and immunity by producing a variety of pluripotent soluble factors, including adipokines (e.g., leptin, resistin, and
Fat factors modulate wound healing
Although the absence of leptin is one of the situations that promotes visceral adiposity and adipokine–cytokine abnormalities that cause hepatic injury and inflammation (i.e., steatohepatitis), a normal fibrogenic response to liver injury does not occur when leptin is absent. Thus, hepatotoxin-treated or Schistosoma-treated ob/ob mice exhibit significantly less liver fibrosis than do similarly treated, leptin-sufficient litter mate controls (Ikejima et al., 2001, Ikejima et al., 2002, Leclercq
Summary and unanswered questions
Obesity potentiates the severity of alcohol-induced liver damage. The mechanisms by which adiposity and ethanol interact to produce hepatic steatosis and steatohepatitis have been studied most extensively. Exacerbation of the proinflammatory state that induces TNF-α activity and hepatic insulin resistance seems to be involved. However, the precise cellular signals that culminate in hepatocyte dysfunction and death remain controversial. There are proponents for increased hepatocyte apoptosis, as
Acknowledgments
This work was supported by the following NIH grants: AA010154-08S1, AA012059-04, and DK53792-04A2.
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