FGF21 mediates the protective effect of fenofibrate against acetaminophen -induced hepatotoxicity via activating autophagy in mice
| Autor: | Yingying Pan, Rongrong Xiong, Xiaokun Li, Yi Zhang, Qianyao Li, Jujia Zheng, Saisai Zhang, Shulin Yang, Xuebo Pan |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Agonist Male FGF21 medicine.drug_class Biophysics Pharmacology medicine.disease_cause Protective Agents Biochemistry 03 medical and health sciences Mice Fenofibrate medicine Autophagy Animals PPAR alpha Receptor Molecular Biology Acetaminophen Liver injury Mice Knockout business.industry digestive oral and skin physiology Cell Biology Analgesics Non-Narcotic medicine.disease Fibroblast Growth Factors Mice Inbred C57BL Oxidative Stress 030104 developmental biology Hepatocytes Chemical and Drug Induced Liver Injury business Oxidative stress medicine.drug |
| Zdroj: | Biochemical and biophysical research communications. 503(2) |
| ISSN: | 1090-2104 |
| Popis: | Overdose of acetaminophen (APAP) induces acute liver injury due in part to destruction of mitochondria and resulted oxidative stress. Recently, FGF21 has been demonstrated to be an endocrine factor to protect liver from oxidative stress. The aim of present study is to explore the role of fibroblast growth factor 21 (FGF21) in the protective effect of fenofibrate, an agonist of peroxisome proliferator-activated receptor alpha (PPARα), against acetaminophen (APAP)-induced liver injury. Mice and primary cultured hepatocytes were used to test the potential hepatoprotective effect of fenofibrate against APAP-induced hepatotoxicity. FGF21 deficient mice were used to evaluate the role of FGF21 in fenofibrate against APAP-induced acute liver injury. Post-treatment with fenofibrate significantly inhibits APAP-induced hepatotoxicity, as evidenced by decreased serum ALT and AST levels and hepatic necrosis in liver tissue as well as increased the surviving rate in response to APAP overdose, whereas this protective effect of fenofibrate is largely attenuated in FGF21 KO mice. Interestingly, administration of fenofibrate efficiently increases autophagy, which was companied with alleviating hepatotoxicity in APAP-treated WT mice. However, such effect is significantly attenuated in APAP-treated FGF21 KO mice. In conclusion, our findings suggest that fenofibrate against APAP-induced hepatotoxicity is at least in part mediated by up-regulating the expression of FGF21, which in turn promotes autophagy-mediated hepatoprotective effects. |
| Databáze: | OpenAIRE |
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