Hepatocyte DUSP14 maintains metabolic homeostasis and suppresses inflammation in the liver

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Siyuan WangYi-Da Tang

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a prevalent and complex disease that confers a high risk of severe liver disorders. Despite such public and clinical health importance, very few effective therapies are currently available for NAFLD. We report a protective function and the underlying mechanism of dual-specificity phosphatase 14 (DUSP14) in NAFLD and related metabolic disorders. Insulin resistance, hepatic lipid accumulation, and concomitant inflammatory responses, key pathological processes involved in NAFLD development, were significantly ameliorated by hepatocyte-specific DUSP14 overexpression (DUSP14-HTG) in high-fat diet (HFD)-induced or genetically obese mouse models. By contrast, specific DUSP14 deficiency in hepatocytes (DUSP14-HKO) aggravated these pathological alterations. We provided mechanistic evidence that DUSP14 directly binds to and dephosphorylates transforming growth factor β-activated kinase 1 (TAK1), resulting in the reduced activation of TAK1 and its downstream signaling molecules c-Jun N-terminal kinase 1 (JNK), p38, and nuclear factor kappa B NF-κB. This effect was further evidenced by the finding that inhibiting TAK1 activity effectively attenuated the deterioration of glucolipid metabolic pheno...Continue Reading

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Citations

Mar 25, 2018·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yichao ZhaoJun Pu
Jun 20, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Chia-Yu YangTse-Hua Tan
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Mar 29, 2019·World Journal of Gastroenterology : WJG·Jiang-Hua ZhouHong-Liang Li
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Feb 16, 2021·Molecular Metabolism·Beatriz CicuéndezGuadalupe Sabio
Apr 4, 2021·Proceedings of the National Academy of Sciences of the United States of America·Ilona Darlyuk-SaadonDavid Engelberg
May 8, 2021·Cellular and Molecular Gastroenterology and Hepatology·Shunjie XiaXiujun Cai
Mar 27, 2021·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yupeng LiuYi-Da Tang
Apr 4, 2019·Gene Expression·Ming-Ming ChenHongliang Li

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