title: Chronic alcohol exposure stimulates adipose tissue lipolysis in mice: role of reverse triglyceride transport in the pathogenesis of alcoholic steatosis.
abstract: 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.affiliation: Department of Nutrition, University of North Carolina at Greensboro, Greensboro, North Carolina.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhong
authors.affiliation: College of Animal Sciences and Veterinary Medicine, Agricultural University of Hebei, Baoding, Hebei, China.
authors.forename: Yantao
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Medicine, University of Louisville, Louisville, Kentucky.
authors.forename: Yunan
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Chemistry, University of Louisville, Louisville, Kentucky.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Chemistry, University of Louisville, Louisville, Kentucky.
authors.forename: Xue
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Chemistry, University of Louisville, Louisville, Kentucky.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Nutrition, University of North Carolina at Greensboro, Greensboro, North Carolina.
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Chemistry, University of Louisville, Louisville, Kentucky.
authors.forename: Xinmin
authors.initials: X
authors.lastname: Yin
authors.affiliation: Department of Nutrition, University of North Carolina at Greensboro, Greensboro, North Carolina.
authors.forename: Xinguo
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Bioinformatics, University of Louisville, Louisville, Kentucky.
authors.forename: Seongho
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Medicine, University of Louisville, Louisville, Kentucky; Department of Pharmacology & Toxicology, University of Louisville, Louisville, Kentucky; Alcohol Research Center, University of Louisville, Louisville, Kentucky; Louisville VAMC, Louisville, Kentucky.
authors.forename: Craig J
authors.initials: CJ
authors.lastname: McClain
authors.affiliation: Department of Chemistry, University of Louisville, Louisville, Kentucky. Electronic address: xiang.zhang@louisville.edu.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Nutrition, University of North Carolina at Greensboro, Greensboro, North Carolina. Electronic address: z_zhou@uncg.edu.
authors.forename: Zhanxiang
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects*; D000818:Animals; D002908:Chronic Disease; D017666:Deuterium Oxide; D015536:Down-Regulation; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D005227:Fatty Acids / Q000378:metabolism; D005235:Fatty Liver, Alcoholic / Q000209:etiology*; D006706:Homeostasis / Q000187:drug effects; D007333:Insulin Resistance / Q000502:physiology; D050356:Lipid Metabolism / Q000187:drug effects; D008066:Lipolysis / Q000187:drug effects*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D005227:Fatty Acids; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014280:Triglycerides; D000431:Ethanol; D051059:PTEN Phosphohydrolase; D017666:Deuterium Oxide