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Pharmacological inhibition or genetic ablation of soluble epoxide hydrolase attenuates obesity‐induced nonalcoholic fatty liver disease
Author(s) -
Zhang Jianan,
Yang Jun,
Wang Weicang,
Yang Haixia,
Sanidad Katherine z.,
Yang SzuHao,
Sukamtoh Elvira,
Zhang Guodong
Publication year - 2018
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.2018.32.1_supplement.560.7
Subject(s) - epoxide hydrolase 2 , nonalcoholic fatty liver disease , endocrinology , cd36 , medicine , triglyceride , fatty liver , oil red o , chemistry , adipose tissue , enzyme , cholesterol , disease , biochemistry , receptor , adipogenesis
The prevalence of nonalcoholic fatty liver disease (NAFLD) in western countries is 20–30%; it is of critical importance to identify new therapeutic target, in order to reduce the risks of NAFLD and associated diseases. Here, we report that the expression of soluble epoxide hydrolase (sEH) is increased in liver tissues of a high‐fat diet‐induced NAFLD model; in addition, pharmacological inhibition or genetic ablation of sEH attenuates high‐fat diet‐induced NAFLD, suggesting that sEH could be a novel therapeutic target of NAFLD. We find that after 8‐week dietary feeding of high‐fat diet (60%cal), the expression of sEH is dramatically increased in liver. To explore the roles of sEH in obesity‐induced NAFLD, we test whether pharmacological inhibition or genetic ablation of sEH affects the development of NAFLD. We find that oral administration of TPPU and t‐ TUCB, which are two different sEH inhibitors, attenuates high‐fat diet‐induced fat accumulation in liver (assess by liver triglyceride analysis, oil red o staining and H&E histology staining), and reduces expressions of pro‐inflammatory genes in liver ( Mcp‐1 and Tnf‐α ). Similar results are observed in sEH knockout mice. Regarding the mechanisms, we find that pharmacological inhibition or genetic ablation of sEH suppresses the expression of Srebf1 , Ppar‐γ , Cd36 and Dgat2 , which play critical roles in lipid synthesis; and increases the expression of Ppar‐α , regulating fatty acid β‐oxidation. Together, these results support that sEH could be a promising therapeutic target for NAFLD, suppressing fat accumulation and inflammation in liver. This could lead to rapid human translations, because the pharmacological inhibitors of sEH are being evaluated in human clinical trials targeting multiple disorders. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .