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SREBP‐1c increases the hepatic inflammatory response in dairy cows with fatty liver through ROS‐mediated NF‐κB pathway
Author(s) -
Li Xinwei,
Liu Guowen
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.804.4
Subject(s) - nefa , fatty liver , sterol regulatory element binding protein , steatosis , medicine , endocrinology , nf κb , proinflammatory cytokine , liver injury , hepatic stellate cell , tumor necrosis factor alpha , inflammation , triglyceride , chemistry , biology , cholesterol , sterol , disease , insulin
Dairy cows with fatty liver displayed hepatic lipid accumulation and 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. Therefore, SREBP‐1c might associate with the overactivation of the hepatic NF‐κB inflammatory pathway in cows with fatty liver. 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 over induced 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. SREBP‐1c‐overexpressing mice also exhibited hepatic steatosis and an over induced 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. Support or Funding Information This work was supported by the National Natural Science Foundation of China (Beijing, China; grant no. 31402265, 31472247, 31460681) SREBP‐1c‐overexpressing mice presented hepatic steatosis and over induced hepatic IκBα/NF‐κB p65 inflammatory pathwaysA: Pathological examination of the liver; B: liver TG content;C: Western blot analysis of key molecules of the SREBP‐1c and TLR/NF‐κB pathway; D: The phosphorylation levels of IκBα and NF‐κB p65; E: TNF‐α, IL‐6 and IL‐1β concentrations. a and b: the same letter indicates no significant difference ( P >0.05), whereas different letters indicate a significant difference ( P <0.05).