β-Adrenergic induction of lipolysis in hepatocytes is inhibited by ethanol exposure.

The Journal of Biological Chemistry
Micah B SchottMark A McNiven

Abstract

In liver steatosis (i.e. fatty liver), hepatocytes accumulate many large neutral lipid storage organelles known as lipid droplets (LDs). LDs are important in the maintenance of energy homeostasis, but the signaling mechanisms that stimulate LD metabolism in hepatocytes are poorly defined. In adipocytes, catecholamines target the β-adrenergic (β-AR)/cAMP pathway to activate cytosolic lipases and induce their recruitment to the LD surface. Therefore, the goal of this study was to determine whether hepatocytes, like adipocytes, also undergo cAMP-mediated lipolysis in response to β-AR stimulation. Using primary rat hepatocytes and human hepatoma cells, we found that treatment with the β-AR agent isoproterenol caused substantial LD loss via activation of cytosolic lipases adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL). β-Adrenergic stimulation rapidly activated PKA, which led to the phosphorylation of ATGL and HSL and their recruitment to the LD surface. To test whether this β-AR-dependent lipolysis pathway was altered in a model of alcoholic fatty liver, primary hepatocytes from rats fed a 6-week EtOH-containing Lieber-DeCarli diet were treated with cAMP agonists. Compared with controls, EtOH-exposed hepatocy...Continue Reading

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Citations

Jun 28, 2018·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Yuri L BoteonSimon C Afford
Nov 11, 2017·Hepatology Communications·Yuan Li, Wen-Xing Ding
Feb 5, 2019·American Journal of Physiology. Gastrointestinal and Liver Physiology·Paul G ThomesCarol A Casey
Apr 17, 2020·Journal of Cell Science·Kristina Drizyte-MillerMark A McNiven
Dec 7, 2019·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Zhipeng LiMark A McNiven
Jun 16, 2019·The Journal of Cell Biology·Ryan J SchulzeMark A McNiven
Oct 22, 2019·Nutrition & Metabolism·Jining YangXiongwen Chen
Aug 3, 2019·American Journal of Physiology. Gastrointestinal and Liver Physiology·Jennifer L GroebnerPamela L Tuma
May 31, 2019·Frontiers in Pharmacology·Li YangTerrence M Donohue
Oct 17, 2019·International Journal of Molecular Sciences·Shengmin YanXiao-Ming Yin
Aug 9, 2019·The Journal of Cell Biology·Micah B SchottMark A McNiven
Dec 9, 2020·Proceedings of the National Academy of Sciences of the United States of America·Ryan J SchulzeMark A McNiven
Oct 15, 2020·Biomolecules·Mohamed ElnagdyLeila Gobejishvili
Feb 21, 2021·Glia·Tina SmoličNina Vardjan
Dec 1, 2019·Liver Research·Ryan J Schulze, Wen-Xing Ding

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