Tianran Shen1, Xu Chen1, Yanping Li1, Xilan Tang2, Xinwei Jiang2, Chao Yu3, Yuanzhu Zheng1, Honghui Guo4, Wenhua Ling5. 1. Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, PR China; Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, PR China. 2. Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, PR China. 3. Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, PR China; Physical examination center, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, PR China. 4. Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, PR China; Department of Nutrition, Henry Fok School of Food Science and Engineering, Shaoguan University, Shaoguan 512005, PR China. 5. Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, PR China; Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, PR China. Electronic address: lingwh@mail.sysu.edu.cn.
Abstract
There is a growing body of evidence that the interleukin-17A (IL-17A) signaling pathway contributes to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, the mechanism by which IL-17A signaling induces hepatocyte injury is unclear. The aim of the present study was to investigate the significance of the IL-17A axis in NAFLD and to explore the role of IL-17A in high-fat diet (HFD)-induced NAFLD in C57BL/6 mice and oleic acid (OA)-induced lipid accumulation in hepatocytes. Firstly, Consistent upregulation of IL-17A was observed in the HFD-induced steatosis mice but not the normal chow-fed control mice. Administration of IL-17A impaired liver function, aggravated hepatic lipid accumulation by inhibiting fatty acid oxidation in the HFD mice. Conversely, inhibition of IL-17A using an anti-IL-17A monoclonal antibody (mAb) significantly attenuated HFD-induced liver injury. Furthermore, IL-17A accelerated hepatic steatosis through activation of the JNK-PPARα pathway in the HFD mice and OA-preloaded hepatocytes. CONCLUSION: The present study demonstrated that a high fat diet induces IL-17A expression, which exacerbates the progression of NAFLD by inhibiting fatty acid β-oxidation and promoting the accumulation of triglycerides (TG).
There is a growing body of evidence that the interleukin-17A (IL-17A) signaling pathway contributes to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, the mechanism by which IL-17A signaling induces hepatocyte injury is unclear. The aim of the present study was to investigate the significance of the IL-17A axis in NAFLD and to explore the role of IL-17A in high-fat diet (HFD)-induced NAFLD in C57BL/6 mice and oleic acid (OA)-induced lipid accumulation in hepatocytes. Firstly, Consistent upregulation of IL-17A was observed in the HFD-induced steatosismice but not the normal chow-fed control mice. Administration of IL-17Aimpaired liver function, aggravated hepatic lipid accumulation by inhibiting fatty acid oxidation in the HFD mice. Conversely, inhibition of IL-17A using an anti-IL-17A monoclonal antibody (mAb) significantly attenuated HFD-induced liver injury. Furthermore, IL-17A accelerated hepatic steatosis through activation of the JNK-PPARα pathway in the HFD mice and OA-preloaded hepatocytes. CONCLUSION: The present study demonstrated that a high fat diet induces IL-17A expression, which exacerbates the progression of NAFLD by inhibiting fatty acid β-oxidation and promoting the accumulation of triglycerides (TG).
Authors: Piero Portincasa; Leonilde Bonfrate; Mohamad Khalil; Maria De Angelis; Francesco Maria Calabrese; Mauro D'Amato; David Q-H Wang; Agostino Di Ciaula Journal: Biomedicines Date: 2021-12-31
Authors: Ricardo Rodríguez-Calvo; Sara Samino; Josefa Girona; Neus Martínez-Micaelo; Pere Ràfols; María García-Altares; Sandra Guaita-Esteruelas; Alexandra Junza; Mercedes Heras; Oscar Yanes; Xavier Correig; Lluis Masana Journal: Biomolecules Date: 2020-09-03