Document Detail


Chronic alcohol exposure stimulates adipose tissue lipolysis in mice: role of reverse triglyceride transport in the pathogenesis of alcoholic steatosis.
MedLine Citation:
PMID:  22234172     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Alcohol consumption induces liver steatosis; therefore, this study investigated the possible role of adipose tissue dysfunction in the pathogenesis of alcoholic steatosis. Mice were pair-fed an alcohol or control liquid diet for 8 weeks to evaluate the alcohol effects on lipid metabolism at the adipose tissue-liver axis. Chronic alcohol exposure reduced adipose tissue mass and adipocyte size. Fatty acid release from adipose tissue explants was significantly increased in alcohol-fed mice in association with the activation of adipose triglyceride lipase and hormone-sensitive lipase. Alcohol exposure induced insulin intolerance and inactivated adipose protein phosphatase 1 in association with the up-regulation of phosphatase and tensin homolog (PTEN) and suppressor of cytokine signaling 3 (SOCS3). Alcohol exposure up-regulated fatty acid transport proteins and caused lipid accumulation in the liver. To define the mechanistic link between adipose triglyceride loss and hepatic triglyceride gain, mice were first administered heavy water for 5 weeks to label adipose triglycerides with deuterium, and then pair-fed alcohol or control diet for 2 weeks. Deposition of deuterium-labeled adipose triglycerides in the liver was analyzed using Fourier transform ion cyclotron mass spectrometry. Alcohol exposure increased more than a dozen deuterium-labeled triglyceride molecules in the liver by up to 6.3-fold. These data demonstrate for the first time that adipose triglycerides due to alcohol-induced hyperlipolysis are reverse transported and deposited in the liver.
Authors:
Wei Zhong; Yantao Zhao; Yunan Tang; Xiaoli Wei; Xue Shi; Wenlong Sun; Xiuhua Sun; Xinmin Yin; Xinguo Sun; Seongho Kim; Craig J McClain; Xiang Zhang; Zhanxiang Zhou
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-01-09
Journal Detail:
Title:  The American journal of pathology     Volume:  180     ISSN:  1525-2191     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-02-20     Completed Date:  2012-04-27     Revised Date:  2012-05-14    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  998-1007     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Affiliation:
Department of Nutrition, University of North Carolina at Greensboro, Greensboro, North Carolina 28081, USA.
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MeSH Terms
Descriptor/Qualifier:
Adipose Tissue / drug effects*
Animals
Chronic Disease
Deuterium Oxide / diagnostic use
Down-Regulation
Ethanol / administration & dosage,  toxicity*
Fatty Acids / metabolism
Fatty Liver, Alcoholic / etiology*
Homeostasis / drug effects
Insulin Resistance / physiology
Lipid Metabolism / drug effects
Lipolysis / drug effects*
Liver / metabolism
Male
Mice
Mice, Inbred C57BL
Organ Size
PTEN Phosphohydrolase / metabolism
Suppressor of Cytokine Signaling Proteins / metabolism
Triglycerides / metabolism
Up-Regulation
Grant Support
ID/Acronym/Agency:
1RC2AA019385/AA/NIAAA NIH HHS; P01AA017103/AA/NIAAA NIH HHS; P30AA019360/AA/NIAAA NIH HHS; R01 GM087735-03/GM/NIGMS NIH HHS; R01 GM087735-04/GM/NIGMS NIH HHS; R01AA015970/AA/NIAAA NIH HHS; R01AA018016/AA/NIAAA NIH HHS; R01AA018844/AA/NIAAA NIH HHS; R01AA018869/AA/NIAAA NIH HHS; R01DK7071765/DK/NIDDK NIH HHS; R01GM087735/GM/NIGMS NIH HHS; R37AA010762/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
0/Fatty Acids; 0/Socs3 protein, mouse; 0/Suppressor of Cytokine Signaling Proteins; 0/Triglycerides; 64-17-5/Ethanol; 7789-20-0/Deuterium Oxide; EC 3.1.3.67/PTEN Phosphohydrolase

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