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Roles of extrahepatic lipolysis and the disturbance of hepatic fatty acid metabolism in TNF-α -induced hepatic steatosis.
Toxicology. 2019 01 01; 411:172-180.T

Abstract

Our previous study showed that both Kupffer cell eliminator (GdCl3) and tumor necrosis factor α (TNF-α) receptor antagonist (etanercept) could partially attenuate binge drinking-induced liver steatosis. Herein, we extended the study by directly investigating the roles of TNF-α on the hepatic fat levels in mice and in HepG2 cells, and explored the underlying mechanisms. SPF male ICR mice were exposed to TNF-α (0.166 mg/kg body weight) with or without phenylisopropyl adenosine (PIA, an anti-lipolytic drug) for 1.5, 3, 6, and 24 h. We found that TNF-α treatment resulted in hepatic triglyceride (TG) elevation at 6 h time point, which was blocked by PIA. TNF-α led to the activation of extrahepatic lipolysis demonstrated by the increase of serum free fatty acid (FFA) level, and the increased protein levels of adipose triglyceride lipase (ATGL) and phosphorylated hormone-sensitive lipase (HSL) in mice epididymal adipose tissues, but had no significant effects on the protein levels of sterol regulatory element binding protein 1c (SREBP-1c) and peroxisomal proliferator activation receptor α (PPAR-α) in mice liver. The in vitro study showed TNF-α treatment could not result in elevation of TG in HepG2 cells, although it indeed brought about a slight activation of SREBP-1c. These results support the hypothesis that TNF-α might make a small contribution to ethanol-induced fatty liver by stimulating extrahepatic lipolysis.

Authors+Show Affiliations

Institute of Toxicology, School of Public Health, Shandong University, 44 Wenhua West Road, Shandong Province, Jinan City, 250012, PR China.Institute of Toxicology, School of Public Health, Shandong University, 44 Wenhua West Road, Shandong Province, Jinan City, 250012, PR China.Institute of Toxicology, School of Public Health, Shandong University, 44 Wenhua West Road, Shandong Province, Jinan City, 250012, PR China.Institute of Toxicology, School of Public Health, Shandong University, 44 Wenhua West Road, Shandong Province, Jinan City, 250012, PR China.Institute of Toxicology, School of Public Health, Shandong University, 44 Wenhua West Road, Shandong Province, Jinan City, 250012, PR China. Electronic address: zengtao@sdu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30359672

Citation

Yang, Rui, et al. "Roles of Extrahepatic Lipolysis and the Disturbance of Hepatic Fatty Acid Metabolism in TNF-α -induced Hepatic Steatosis." Toxicology, vol. 411, 2019, pp. 172-180.
Yang R, Guan MJ, Zhao N, et al. Roles of extrahepatic lipolysis and the disturbance of hepatic fatty acid metabolism in TNF-α -induced hepatic steatosis. Toxicology. 2019;411:172-180.
Yang, R., Guan, M. J., Zhao, N., Li, M. J., & Zeng, T. (2019). Roles of extrahepatic lipolysis and the disturbance of hepatic fatty acid metabolism in TNF-α -induced hepatic steatosis. Toxicology, 411, 172-180. https://doi.org/10.1016/j.tox.2018.10.011
Yang R, et al. Roles of Extrahepatic Lipolysis and the Disturbance of Hepatic Fatty Acid Metabolism in TNF-α -induced Hepatic Steatosis. Toxicology. 2019 01 1;411:172-180. PubMed PMID: 30359672.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Roles of extrahepatic lipolysis and the disturbance of hepatic fatty acid metabolism in TNF-α -induced hepatic steatosis. AU - Yang,Rui, AU - Guan,Min-Jie, AU - Zhao,Ning, AU - Li,Ming-Jun, AU - Zeng,Tao, Y1 - 2018/10/22/ PY - 2018/07/13/received PY - 2018/09/16/revised PY - 2018/10/20/accepted PY - 2018/10/26/pubmed PY - 2019/5/16/medline PY - 2018/10/26/entrez KW - Alcoholic fatty liver KW - Hormone-sensitive lipase KW - Lipolysis KW - Phenylisopropyl adenosine KW - TNF-α SP - 172 EP - 180 JF - Toxicology JO - Toxicology VL - 411 N2 - Our previous study showed that both Kupffer cell eliminator (GdCl3) and tumor necrosis factor α (TNF-α) receptor antagonist (etanercept) could partially attenuate binge drinking-induced liver steatosis. Herein, we extended the study by directly investigating the roles of TNF-α on the hepatic fat levels in mice and in HepG2 cells, and explored the underlying mechanisms. SPF male ICR mice were exposed to TNF-α (0.166 mg/kg body weight) with or without phenylisopropyl adenosine (PIA, an anti-lipolytic drug) for 1.5, 3, 6, and 24 h. We found that TNF-α treatment resulted in hepatic triglyceride (TG) elevation at 6 h time point, which was blocked by PIA. TNF-α led to the activation of extrahepatic lipolysis demonstrated by the increase of serum free fatty acid (FFA) level, and the increased protein levels of adipose triglyceride lipase (ATGL) and phosphorylated hormone-sensitive lipase (HSL) in mice epididymal adipose tissues, but had no significant effects on the protein levels of sterol regulatory element binding protein 1c (SREBP-1c) and peroxisomal proliferator activation receptor α (PPAR-α) in mice liver. The in vitro study showed TNF-α treatment could not result in elevation of TG in HepG2 cells, although it indeed brought about a slight activation of SREBP-1c. These results support the hypothesis that TNF-α might make a small contribution to ethanol-induced fatty liver by stimulating extrahepatic lipolysis. SN - 1879-3185 UR - https://www.unboundmedicine.com/medline/citation/30359672/Roles_of_extrahepatic_lipolysis_and_the_disturbance_of_hepatic_fatty_acid_metabolism_in_TNF_α__induced_hepatic_steatosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0300-483X(18)30149-5 DB - PRIME DP - Unbound Medicine ER -