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Journal of Zhejiang University SCIENCE B 1998 Vol.-1 No.-1 P.

http://doi.org/10.1631/jzus.B2200562


Fibroblast growth factor 21 attenuates tacrolimus-induced hepatic lipid accumulation through TFEB-regulated lipophagy


Author(s):  Zhensheng ZHANG, Li XU, Xun QIU, Xinyu YANG, Zhengxing LIAN, Xuyong WEI, Di LU, Xiao XU

Affiliation(s):  Zhejiang University School of Medicine, Hangzhou 310058, China; more

Corresponding email(s):   zjxu@zju.edu.cn

Key Words:  Autophagy, Fibroblast growth factor 21, Lipid, Lipophagy, Lysosome, Tacrolimus, TFEB


Zhensheng ZHANG, Li XU, Xun QIU, Xinyu YANG, Zhengxing LIAN, Xuyong WEI, Di LU, Xiao XU. Fibroblast growth factor 21 attenuates tacrolimus-induced hepatic lipid accumulation through TFEB-regulated lipophagy[J]. Journal of Zhejiang University Science B, 1998, -1(-1): .

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%A Di LU
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A1 - Zhengxing LIAN
A1 - Xuyong WEI
A1 - Di LU
A1 - Xiao XU
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PB - Zhejiang University Press & Springer
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DOI - 10.1631/jzus.B2200562


Abstract: 
tacrolimus (TAC), also called FK506, is one of the classical immunosuppressants to prevent allograft rejection after liver transplantation. However, it has been proved to be associated with post-transplant hyperlipemia. The mechanism behind this is unknown, and it is urgent to explore preventive strategies for hyperlipemia after transplantation. Therefore, we established a hyperlipemia mouse model to investigate the mechanism, by injecting TAC intraperitoneally for 8 weeks. After TAC treatment, the mice developed hyperlipemia (manifested as elevated TG and LDL-c) as well as decreased HDL-c. Accumulation of lipid droplets was observed in the liver. In addition to lipid accumulation, TAC induced inhibition of the autophagy-lysosome pathway (LC3B II/I and LC3B II/Actin ratio, TFEB, P62 and LAMP1) and downregulation of FGF21 in vivo. Overexpression of FGF21 may reverse TAC-induced TG accumulation. In this mouse model, the recombinant FGF21 protein ameliorated hepatic lipid accumulation and hyperlipemia through repair of the autophagy-lysosome pathway. We conclude that TAC downregulates FGF21 and thus exacerbates lipid accumulation by impairing the autophagy-lysosome pathway. Recombinant FGF21 protein treatment could therefore reverse TAC-caused lipid accumulation and hypertriglyceridemia by enhancing autophagy.

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