Interleukin-17A exacerbates high-fat diet-induced hepatic steatosis by inhibiting fatty acid β-oxidation.
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.



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).
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.
Tianran
T
Shen
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.
Xu
X
Chen
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.
Yanping
Y
Li
Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, PR China.
Xilan
X
Tang
Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, PR China.
Xinwei
X
Jiang
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.
Chao
C
Yu
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.
Yuanzhu
Y
Zheng
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.
Honghui
H
Guo
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.
Wenhua
W
Ling
D000818:Animals; D004041:Dietary Fats / Q000009:adverse effects* / Q000494:pharmacology; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008297:Male; D051379:Mice; D065626:Non-alcoholic Fatty Liver Disease / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D019301:Oleic Acid / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D047493:PPAR alpha / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014280:Triglycerides / Q000378:metabolism
D004041:Dietary Fats; C098680:Il17a protein, mouse; D020381:Interleukin-17; D047493:PPAR alpha; D014280:Triglycerides; D019301:Oleic Acid; D048670:MAP Kinase Kinase 4
Fatty acid metabolism; Inflammation; JNK-PPARα; NAFLD