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FGF21 ameliorates nonalcoholic fatty liver disease by inducing autophagy

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Abstract

The aim of this study is to evaluate the role of fibroblast growth factor 21 (FGF21) in nonalcoholic fatty liver disease (NAFLD) and seek to determine if its therapeutic effect is through induction of autophagy. In this research, Monosodium L-glutamate (MSG)-induced obese mice or normal lean mice were treated with vehicle, Fenofibrate, and recombinant murine FGF21, respectively. After 5 weeks of treatment, metabolic parameters including body weight, blood glucose and lipid levels, hepatic and fat gene expression levels were monitored and analyzed. Also, fat-loaded HepG2 cells were treated with vehicle or recombinant murine FGF21. The expression levels of proteins associated with autophagy were detected by western blot, real-time PCR, and transmission electron microscopy (TEM). Autophagic flux was monitored by laser confocal microscopy and western blot. Results showed that FGF21 significantly reduced body weight (P < 0.01) and serum triglyceride, improved insulin sensitivity, and reversed hepatic steatosis in the MSG model mice. In addition, FGF21 significantly increased the expression of several proteins related to autophagy both in MSG mice and fat-loaded HepG2 cells, such as microtubule associated protein 1 light chain 3, Bcl-2-interacting myosin-like coiled-coil protein-1 (Beclin-1), and autophagy-related gene 5. Furthermore, the evidence of TEM revealed an increased number of autophagosomes and lysosomes in the model cells treated with FGF21. In vitro experimental results also showed that FGF21 remarkably increased autophagic flux. Taken together, FGF21 corrects multiple metabolic parameters on NAFLD in vitro and in vivo by inducing autophagy.

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Acknowledgments

We thank Ph.D. Lubna M. Rasool for helpful revising. This work was supported by Heilongjiang Development and Reform Commission ([2011]1570), National Natural Science Foundation of China (J1210069/J0106), the key scientific research programs of Henan education department (No. 16A180007) and PhD scientific research initiation foundation of Henan normal university (No. 5101049170162 and No. 5201319170001).

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    Authors and Affiliations

    1. School of Life Science, Northeast Agricultural University, Harbin, China

      Shenglong Zhu, Yunzhou Wu, Lei Ma, Dan Yu, Yuquan Wei, Guiping Ren & Deshan Li

    2. State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, China

      Shenglong Zhu & Guangxiao Lin

    3. School of Life Science, Henan Normal University, Xinxiang, China

      Xianlong Ye & Jianying Qi

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    Shenglong Zhu, Yunzhou Wu and Xianlong Ye contributed equally to this study.

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    Zhu, S., Wu, Y., Ye, X. et al. FGF21 ameliorates nonalcoholic fatty liver disease by inducing autophagy. Mol Cell Biochem 420, 107–119 (2016). https://doi.org/10.1007/s11010-016-2774-2

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