Effect of Ethanol on Lipid Metabolism

Hepatic lipid metabolism is a series of complex processes that control influx and efflux of not only hepatic lipid pools, but also organismal pools. Lipid homeostasis is usually tightly controlled by expression, substrate supply, oxidation and secretion that keep hepatic lipid pools relatively constant. However, perturbations of any of these processes can lead to lipid accumulation in the liver. Although it is thought that these responses are hepatic arms of the 'thrifty genome', they are maladaptive in the context of chronic fatty liver diseases. Ethanol is likely unique among toxins, in that it perturbs almost all aspects of hepatic lipid metabolism. This complex response is due in part to the large metabolic demand placed on the organ by alcohol metabolism, but also appears to involve more nuanced changes in expression and substrate supply. The net effect is that steatosis is a rapid response to alcohol abuse. Although transient steatosis is largely an inert pathology, the chronicity of alcohol-related liver disease seems to require steatosis. Better and more specific understanding of the mechanisms by which alcohol causes steatosis may therefore translate into targeted therapies to treat alcohol-related liver disease and/or prevent its progression.