Ethanol and C2 ceramide activate fatty acid oxidation in human hepatoma cells

Scientific Reports
Jason M CorrentiRotonya M Carr

Abstract

Obesogenic lipids and the sphingolipid ceramide have been implicated as potential cofactors in alcoholic liver disease (ALD) patients. However, the mechanisms by which these lipids modulate lipid trafficking in ethanol-treated human liver cells to promote steatosis, an early stage of ALD, are poorly understood. We measured fatty acid (FA) uptake, triglyceride export, FA synthesis and FA oxidation in human hepatoma (VL-17A) cells in response to ethanol and the exogenous lipids oleate, palmitate and C2 ceramide. We found that in combination with ethanol, both oleate and palmitate promote lipid droplet accumulation while C2 ceramide inhibits lipid droplet accumulation by enhancing FA oxidation. Further, using both a pharmacologic and siRNA approach to reduce peroxisome proliferator-activated receptors α (PPARα) gene expression, we demonstrate that C2 ceramide abrogates ethanol-mediated suppression of FA oxidation through an indirect PPARα mechanism. Together, these data suggest that lipids interact differentially with ethanol to modulate hepatocellular lipid droplet accumulation and may provide novel targets for preventing the earliest stage of alcoholic liver disease, alcoholic steatosis.

References

Apr 15, 1977·The Biochemical Journal·M J SavolainenI E Hassinen
Feb 1, 1989·Alcoholism, Clinical and Experimental Research·A A NanjiS W French
May 15, 1988·Archives of Biochemistry and Biophysics·C E WolflaD W Crabb
Jan 1, 1986·Alcoholism, Clinical and Experimental Research·N Grunnet, J Kondrup
Nov 1, 1983·The British Journal of Nutrition·C CascalesA Santos-Ruiz
Aug 1, 1995·Gastroenterology·A A NanjiA J Dannenberg
Jun 10, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·C P Day, O F James
Mar 30, 1999·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·A GalliD Crabb
Mar 4, 2000·Toxicology in Vitro : an International Journal Published in Association with BIBRA·U ZanelliP G Gervasi
Mar 10, 2001·Life Sciences·M P CarrascoJ L Segovia
Apr 3, 2001·Journal of Hepatology·L M FragoI Varela-Nieto
Aug 1, 1961·The Journal of Clinical Investigation·G REBOUCAS, K J ISSELBACHER
Feb 1, 1961·The Journal of Clinical Investigation·C S LIEBER, R SCHMID
Jun 15, 2004·American Journal of Physiology. Gastrointestinal and Liver Physiology·Min You, David W Crabb
Aug 19, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Min YouDavid W Crabb
Sep 27, 2005·The International Journal of Biochemistry & Cell Biology·Terrence M DonohueDahn L Clemens
Feb 3, 2006·Journal of Biochemistry·Saeko TakedaYasuyuki Igarashi
Apr 20, 2006·Archives of Biochemistry and Biophysics·Yingjun Luan, Helen R Griffiths
Mar 18, 2008·Alcoholism, Clinical and Experimental Research·Ki M MakCharles S Lieber
May 12, 2009·The Journal of Biological Chemistry·Yan J JiangKenneth R Feingold
Dec 25, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Robert S O'SheaUNKNOWN Practice Parameters Committee of the American College of Gastroenterology
Mar 13, 2010·American Journal of Physiology. Gastrointestinal and Liver Physiology·Suthat LiangpunsakulDavid W Crabb
Jul 28, 2010·Gastroenterology·Wen-Xing DingXiao-Ming Yin
Nov 10, 2010·Alcoholism, Clinical and Experimental Research·Zhenwen ZhaoSuthat Liangpunsakul
Nov 3, 2011·The Journal of Clinical Investigation·Benjamin T Bikman, Scott A Summers
Dec 24, 2011·American Journal of Physiology. Gastrointestinal and Liver Physiology·Suthat LiangpunsakulDavid W Crabb
May 12, 2012·Oxidative Medicine and Cellular Longevity·Lisa LongatoSuzanne M de la Monte
Aug 30, 2012·Nature Methods·Caroline A SchneiderKevin W Eliceiri
Oct 24, 2012·Autophagy·Paul G ThomesTerrence M Donohue
Nov 16, 2012·Journal of Lipid Research·Megan M YoungHong-Gang Wang
Feb 13, 2013·Alcoholism, Clinical and Experimental Research·Rotonya M CarrRexford S Ahima
Jan 25, 2014·International Journal of Experimental Pathology·Ming TongSuzanne M de la Monte
Apr 20, 2014·American Journal of Physiology. Gastrointestinal and Liver Physiology·Jason M CorrentiJan B Hoek

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Citations

Feb 8, 2020·Journal of Lipid Research·Sookyoung Jeon, Rotonya Carr
Feb 11, 2021·Nutrients·Julia TraubVanessa Stadlbauer
Dec 1, 2019·Liver Research·Ryan J Schulze, Wen-Xing Ding

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Methods Mentioned

BETA
Assay
transfection
pharmacotherapies

Software Mentioned

ImageJ
Cignal
NeoLynx
GraphPad Prism

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