Targeting DUSP7 signaling alleviates hepatic steatosis, inflammation and oxidative stress in high fat diet (HFD)-fed mice via suppression of TAK1
Authors: Ling Guo
Yongcun Liu
Yuan Zhao
Meng Li
Liping Wu
Journal: Free Radical Biology and Medicine (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: DUSP7; Dyslipidemia; Inflammatory response and ROS; NAFLD; TAK1.

Abstract:  The non-alcoholic fatty liver disease (NAFLD), as a critical liver disease, is still lack of effective treatments because the molecular mechanism revealing the NAFLD pathogenesis remains unclear. Dual specific phosphatase 6 (DUSP7) shows effects on inflammatory response and is a negative feedback mechanism of the mitogen-activated protein kinase (MAPK) superfamily, which are critical factors in regulating NAFLD progression. However, the effects of DUSP7 on hepatic steatosis are still not fully understood. Here, we found that DUSP7 functioned as a negative regulator of NAFLD and in various metabolic disorders. DUSP7 expression was markedly reduced in liver samples from patients with simple hepatic steatosis or non-alcoholic steatohepatitis (NASH), as well as in liver tissues from high fat diet (HFD)-challenged mice or genetically obese (ob/ob) mice. DUSP7 knockout markedly accelerated insulin resistance, glucose intolerance, liver dysfunction, fibrosis and hepatic steatosis in HFD-fed mice. In addition, inflammatory response was significantly exacerbated in HFD-challenged mice with DUSP7 deletion, which was associated with the elevated activation of nuclear factor-κB (NF-κB) and MAPKs signaling pathways. Moreover, oxidative stress was detected in liver of HFD-induced mice, and this phenomenon was aggravated in mice with DUSP7 knockout. Importantly, we demonstrated that DUSP7 physically interacted with transforming growth factor β (TGF-β)-activated kinase (TAK1). DUSP7 deletion considerably promoted the activation of TAK1 in mice after HFD feeding, contributing to the lipid deposition, inflammatory response and reactive oxygen species (ROS) production. Taken together, DUSP7 might function as a protective factor against NAFLD development and metabolic disorder through alleviating dyslipidemia, inflammation and oxidative stress by directly interacting with TAK1 in hepatocytes, which was involved in the suppression of fibrosis. Thus, we may provide an effective strategy for the treatment of hepatic steatosis via targeting DUSP7. 

Retracted: No

PubPeer comments:
  phosphorescent detection of acetone and treatment effect on catheter-associated infections  It s a floor polish AND a dessert topping! ------------------------- If the References are any guide, the authors were unsure whether they were studying catheter-associated infections, squamous-cell carcinoma, or algorithms for RFID tags.  Hemodialysis brings hope for patients at the end-stage of renal disease (ESRD), and the establishment of vascular access is a substitute for maintenance hemodialysis [1]. - [1] M. Zhou, Y. Li, S. Lin, Y. Chen, Y. Qian, Z. Zhao, H. Fan. Dig. Dis. Sci., 64, 2147 (2019). ** H3K9me3, H3K36me3, and H4K20me3 expression correlates with patient outcome in esophageal squamous cell carcinoma as epigenetic markers **  A vein indwelling catheter has been widely used in clinical practice because of its advantage of rapid establishment, small damage and good preventive effect [2]. - [2] S. Lin, M. Zhou, Y. Li, Y. Chen, W. Xu, W. Xia, S. Wang, R. Yin, Q. Zhang, L. Xu. Int. J. Clin. Exp. Patho, 12, 2657 (2019). ** H3K27 trimethylation and H3K9 dimethylation as poor prognostic markers for patients with esophageal squamous cell carcinoma **  However, as the dialysis catheter retention time increases, the corresponding complications also increase, and catheter-related infections have been one of the most serious complications [3]. - [3] J. Su, Z. Sheng, A. Liu, Y. Han, Y. Chen. IEEE Trans. Commun., 68, 998 (2020). ** A group-based binary splitting algorithm for UHF RFID anti-collision systems ** ,