Kupffer cells activation promoted binge drinking-induced fatty liver by activating lipolysis in white adipose tissues. (1st September 2017)

• Record Type: Journal Article
• Authors: Zhao, Yu-Ying; Yang, Rui; Xiao, Mo; Guan, Min-Jie; Zhao, Ning; Zeng, Tao
• Is Part Of: Toxicology. Volume 390(2017)
• Page Start: 53
• Page End: 60
• Publication Date: 2017-09-01
• Subjects: ACC acyl-CoA carboxylase -- ACOX acetyl-CoA oxidase -- AFL alcoholic fatty liver -- ALD alcoholic liver disease -- ALT alanine aminotransferase -- AST aspartate aminotransferase -- AMPK AMP-activated protein kinase -- CPT-1 carnitine palmitoyltransferase 1 -- CYP2E1 cytochrome P4502E1 -- FAS fatty acid synthase -- FFA free fatty acid -- HSL hormone-sensitive lipase -- KCs Kupffer cell -- LFABP liver fatty acid binding protein -- LPS lipopolysaccharide -- MDA malondialdehyde -- NO nitric oxide -- PPAR-α peroxisomal proliferator activation receptor α -- ROS reactive oxygen species -- SREBP-1c sterol regulatory element binding protein 1c -- TG triglyceride -- TNF-α tumor necrosis factor α; Alcoholic fatty liver -- TNF-α -- GdCl3 -- Etanercept -- Fat mobilization; Toxicology -- Periodicals; Chemicals -- Physiological effect -- Periodicals; 615.9005
• DOI: 10.1016/j.tox.2017.09.001
• Languages: English
• ISSNs: 0300-483X

Abstract

Graphical abstract: Highlights: GdCl3 and etanercept attenuated binge drinking-induced hepatic TG accumulation by a similar amount. GdCl3 and etanercept had no effects on ethanol-induced disturbance of PPAR-α and SREBP-1c. GdCl3 and etanercept suppressed binge drinking-induced phosphorylation of HSL. TNF-α promoted HSL phosphorylation and lipolysis in cultured epididymal adipose tissues. Abstract: Kupffer cells (KCs) have been suggested to play critical roles in chronic ethanol induced early liver injury, but the role of KCs in binge drinking-induced hepatic steatosis remains unclear. This study was designed to investigate the roles of KCs inhibitor (GdCl3 ) and TNF-α antagonist (etanercept) on binge drinking-induced liver steatosis and to explore the underlying mechanisms. C57BL/6 mice were exposed to three doses of ethanol (6 g/kg body weight) to mimic binge drinking-induced fatty liver. The results showed that both GdCl3 and etanercept partially but significantly alleviated binge drinking-induced increase of hepatic triglyceride (TG) level, and reduced fat droplets accumulation in mice liver. GdCl3 but not etanercept significantly blocked binge drinking-induced activation of KCs. However, neither GdCl3 nor etanercept could affect binge drinking-induced decrease of PPAR-α, ACOX, FAS, ACC and SCD protein levels, or increase of the LC3 II/LC3 I ratio and p62 protein level. Interestingly, both GdCl3 and etanercept significantly suppressed binge drinking-induced phosphorylation of HSL in epididymal adipose tissues. Results of i n vitro studies with cultured epididymal adipose tissues showed that TNF-α could increase the phosphorylation of HSL in adipose tissues and upgrade the secretion of free fatty acid (FFA) in the culture medium. Taken together, KCs inhibitor and TNF-α antagonist could partially attenuate binge drinking-induced liver steatosis, which might be attributed to the suppression of mobilization of white adipose tissues. These results suggest that KCs activation may promote binge drinking-induced fatty liver by TNF-α mediated activation of lipolysis in white adipose tissues.