Avances lipidos

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Hindawi Publishing Corporation International Journal of Hepatology Volume 2012, Article ID 978136, 8 pages doi:10.1155/2012/978136

Research Article Lipid Droplet Accumulation and Impaired Fat Efflux in Polarized Hepatic Cells: Consequences of Ethanol Metabolism
Benita L. McVicker,1, 2 Karuna Rasineni,1, 2 Dean J. Tuma,1, 2 Mark A. McNiven,3 and Carol A. Casey1, 2
1 Liver

StudyUnit-Research Service (151), VA Nebraska-Western Iowa Health Care System, 4101 Woolworth Avenue, Omaha, NE 68105, USA 2 Departments of Internal Medicine and Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA 3 Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA Correspondence should be addressed to Carol A.Casey, ccasey@unmc.edu Received 12 September 2011; Revised 22 November 2011; Accepted 8 December 2011 Academic Editor: Angela Dolganiuc Copyright © 2012 Benita L. McVicker et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Steatosis, an early manifestation in alcoholic liver disease, is associated with the accumulation of hepatocellular lipid droplets (LDs). However, the role ethanol metabolism has in LD formation and turnover remains undefined. Here, we assessed LD dynamics following ethanol and oleic acid treatment to ethanol-metabolizing WIF-B cells (a hybrid of human fibroblasts (WI 38) and Fao rat hepatoma cells). An OAdose-dependent increase in triglyceride and stained lipids was identified which doubled (P < 0.05) in the presence of ethanol. This effect was blunted with the inclusion of an alcohol metabolism inhibitor. The ethanol/ OA combination also induced adipophilin, LD coat protein involved in the attenuation of lipolysis. Additionally, ethanol treatment resulted in a significant reduction in lipid efflux.These data demonstrate that the metabolism of ethanol in hepatic cells is related to LD accumulation, impaired fat efflux, and enhancements in LD-associated proteins. These alterations in LD dynamics may contribute to ethanol-mediated defects in hepatocellular LD regulation and the formation of steatosis.

1. Introduction
Alcohol abuse and alcoholic liver disease (ALD) are major health problemsboth in the USA and worldwide. The most prevalent manifestations of ALD are the presence of fatty liver (hepatic steatosis), alcoholic hepatitis, and cirrhosis. Of these manifestations, it is noted that hepatic steatosis is a reversible early stage of ALD whose presence has been related to the liver’s enhanced sensitivity to damaging triggers such as oxidative stress and endotoxins [1, 2]. Thus, theaberrant content of lipids in hepatocytes can act as a key “first hit” in the progression of ALD making lipid accumulation a prime target for therapeutic intervention. Remarkably, little is known about the regulatory mechanisms involved in the accumulation of intracellular lipids which are stored in dynamic organelles called lipid droplets (LDs). Furthermore, it is unclear how LD formation,degradation (lipolysis), or

export is affected, particularly in the hepatocyte by the adverse effects of alcohol exposure and the metabolism of ethanol. The organelle identified as having a central role in the accumulation of lipids in hepatocytes is the LD. LDs are intracellular stores of neutral lipids, predominately cholesterol esters, and triglycerides that are bound by a phospholipid monolayer [3].Long considered to be inert, LDs have recently attracted great interest as dynamic structures at the hub of lipid and energy metabolism. In general, LDs are thought to originate from the endoplasmic reticulum from where they are trafficked through the cytoplasm, interacting with various organelles and transporting lipids as the energy needs of the cell dictate [4, 5]. In the healthy liver, LDs in...
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