title: SREBP-1c overactivates ROS-mediated hepatic NF-κB inflammatory pathway in dairy cows with fatty liver.
abstract: Dairy cows with fatty liver are characterized by hepatic lipid accumulation and a severe inflammatory response. Sterol receptor element binding protein-1c (SREBP-1c) and nuclear factor κB (NF-κB) are components of the main pathways for controlling triglyceride (TG) accumulation and inflammatory levels, respectively. A previous study demonstrated that hepatic inflammatory levels are positively correlated with hepatic TG content. We therefore speculated that SREBP-1c might play an important role in the overactivation of the hepatic NF-κB inflammatory pathway in cows with fatty liver. Compared with healthy cows, cows with fatty liver exhibited severe hepatic injury and high blood concentrations of the inflammatory cytokines TNF-α, IL-6 and IL-1β. Hepatic SREBP-1c-mediated lipid synthesis and the NF-κB inflammatory pathway were both overinduced in cows with fatty liver. In vitro, treatment with non-esterified fatty acids (NEFA) further increased SREBP-1c expression and NF-κB pathway activation, which then promoted TG and inflammatory cytokine synthesis. SREBP-1c overexpression overactivated the NF-κB inflammatory pathway in hepatocytes by increasing ROS content and not through TLR4. Furthermore, SREBP-1c silencing decreased ROS content and further attenuated the activation of the NEFA-induced NF-κB pathway, thereby decreasing TNF-α, IL-6 and IL-1β synthesis. SREBP-1c-overexpressing mice exhibited hepatic steatosis and an overinduced hepatic NF-κB pathway. Taken together, these results indicate that SREBP-1c enhances the NEFA-induced overactivation of the NF-κB inflammatory pathway by increasing ROS in cow hepatocytes, thereby further increasing hepatic inflammatory injury in cows with fatty liver.
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, 130062 Jilin, China.
authors.forename: Xinwei
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, 130062 Jilin, China.
authors.forename: Weikun
authors.initials: W
authors.lastname: Huang
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, 130062 Jilin, China.
authors.forename: Jingmin
authors.initials: J
authors.lastname: Gu
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, 130062 Jilin, China.
authors.forename: Xiliang
authors.initials: X
authors.lastname: Du
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, 130062 Jilin, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lei
authors.affiliation: College of Animal Science and Technology, Inner Mongolia National University, Tongliao 028042, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Yuan
authors.affiliation: College of Animal Science and Technology, Inner Mongolia National University, Tongliao 028042, China.
authors.forename: Guoquan
authors.initials: G
authors.lastname: Sun
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, 130062 Jilin, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, 130062 Jilin, China. Electronic address: xbli@jlu.edu.cn.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, 130062 Jilin, China. Electronic address: liuguowen2008@163.com.
authors.forename: Guowen
authors.initials: G
authors.lastname: Liu
mesh_terms: D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D005234:Fatty Liver / Q000276:immunology / Q000378:metabolism / Q000662:veterinary*; D005260:Female; D022781:Hepatocytes / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D051780:Sterol Regulatory Element Binding Protein 1; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA
keywords: Dairy cows; Fatty liver; Non-esterified fatty acids; Nuclear factor κB; Sterol receptor element binding protein-1c