Chitinase-3-like-1 deficiency attenuates ethanol-induced liver injury by inhibition of sterol regulatory element binding protein 1-dependent triglyceride synthesis

• Published in: Metabolism, clinical and experimental Vol. 95; pp. 46 - 56
• Main Authors: Lee, Dong Hun, Han, Ji Hye, Lee, Yong Sun, Jung, Young Suk, Roh, Yoon Seok, Yun, Jae Suk, Han, Sang Bae, Hong, Jin Tae
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2019
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2019.03.010

Alcohol overconsumption and abuse lead to alcoholic liver disease (ALD), which is a major chronic liver disease worldwide. Chitinase-3-like protein 1 (CHI3L1) have an important role in the pathogenesis of inflammatory disease. However, the role of CHI3L1 in ALD has not yet been reported. In the present study, we investigated the effect of CHI3L1 on chronic plus binge ethanol-induced liver injury. CHI3L1 knock out (KO) mice and their littermate control mice based on C57BL/6 (10–12 weeks old) were fed on a Lieber-DeCarli diet containing 6.6% ethanol for 10 days. And, CHI3L1 siRNA or CHI3L1 expressing vector was transfected HepG2 cells were treated with ethanol or without. Ethanol-induced hepatic triglyceride (TG) levels and the mRNA levels of TG synthesis-related genes such as acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS) and stearoyl-CoA desaturase-1 (SCD1) were decreased in the liver of CHI3L1 knock out (KO) mice and the HepG2 cells transfected with CHI3L1 siRNA. Increased mRNA level and activation of SREBP1 which is transcription factor of ACC, FAS and SCD1 by ethanol feeding were reduced in the liver of ethanol-fed CHI3L1 KO mice. Moreover, ethanol-induced SREBP1 luciferase activity and mRNA level of SREBP1, ACC, FAS and SCD1 were also decreased in the HepG2 cells transfected with CHI3L1 siRNA, while those were further increased in the HepG2 cells treated with recombinant human CHI3L1. Furthermore, oxidative stress and up-regulated pro-inflammatory cytokines by ethanol were recovered in the liver of ethanol-fed CHI3L1 KO mice. Our finding suggest that inhibition of CHI3L1 suppressed ethanol-induced liver injury through inhibition of TG synthesis, and the blocking of oxidative stress and hepatic inflammation induced SREBP1 activity could be significant. •Ethanol-induced liver injury was ameliorated in CHI3L1 KO mice.•Ethanol-induced oxidative stress and inflammation in the liver were attenuated in CHI3L1 KO mice.•CHI3L1 KO mice showed inhibition of ethanol-induced SREBP1 in the liver.•Ethanol-induced oxidative stress and inflammation were inhibited in HepG2 cells by CHI3L1 si-RNA transfection.