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Mice lacking myotubularin-related protein 14 show accelerated high-fat diet-induced lipid accumulation and inflammation

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Abstract

The phosphoinositide phosphatase, myotubularin-related protein 14 (MTMR14), has been reported to play an important role in the regulation of muscle performance, autophagy, and aging in mice. We previously showed that MTMR14-knockout (KO) mice gain weight earlier than their wild-type (WT) littermates even on a normal chow diet (NCD), suggesting that this gene might also be involved in regulating metabolism. In the present study, we evaluated the effect of MTMR14 deficiency on high-fat diet (HFD)-induced obesity, lipid accumulation, metabolic disorders, and inflammation in WT and MTMR14-KO mice fed with NCD or HFD. To this end, MTMR14-KO mice fed with HFD showed significantly increased body weight, blood glucose levels, serum triglyceride (TG) levels, and total cholesterol (TC) levels as compared to their age-matched WT control. Additionally, lipid accumulation also increased in the KO mice. Simultaneously, the expression of metabolism-associated genes (Glut4, adiponectin, and leptin) was different in the liver, muscle, and fatty tissue of MTMR14-KO mice fed with HFD. More importantly, the expression of several inflammation-associated genes (TNF-α, IL-6, IL-1β, and MCP-1) dramatically increased in the liver, muscle, and fatty tissue of MTMR14-KO mice relative to control. Taken together, these results suggest that MTMR14 deficiency accelerates HFD-induced metabolic dysfunction and inflammation. Furthermore, the results showed that exacerbated metabolic dysfunction and inflammation may be regulated via the PI3K/Akt and ERK signaling pathways.

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Acknowledgments

We would like to thank Dr. Cheng-Kui Qu from Case Western Reserve University for providing MTMR14+/− mice. This project was supported by the Fund for Distinguished Young Scholars of Heibei Province to Jinhua Shen (Grant No. 2012FFA028), Technology Foundation for Selected Overseas Chinese Scholar of Ministry of Personnel of China, National Natural Science Foundation of China (Grant No. 81170227 to Jinhua Shen; 30900816 and 31371307 to Yong-bo Peng), and the Natural Science Foundation of Hubei Province (Grant No. 2014CFC1116 to Yong-bo Peng).

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    Authors and Affiliations

    1. Institute For Medical Biology and Hubei Provincial Key Laboratory for Protection and Application of Special Plants in Wuling Area of China, College of Life Sciences, South-Central University for Nationalities, Wuhan, 430074, China

      Lv Yin, Peng Yong-bo, Yu Meng-Fei, Chen Weiwei, Zhao Ping, Xue Lu, Ma Li-Qun, Liu Qing-hua & Shen Jinhua

    2. Wuhan Youzhiyou Biopharmaceutical Co., Ltd., 666 Gaoxin Rd, Biolake, Wuhan, 430075, China

      Cai Congli

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    1. Lv Yin
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    Correspondence to Liu Qing-hua or Shen Jinhua.

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    Lv Yin and Peng Yong-bo contributed equally to this work.

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    Yin, L., Yong-bo, P., Meng-Fei, Y. et al. Mice lacking myotubularin-related protein 14 show accelerated high-fat diet-induced lipid accumulation and inflammation. J Physiol Biochem 73, 17–28 (2017). https://doi.org/10.1007/s13105-016-0520-6

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    • DOI: https://doi.org/10.1007/s13105-016-0520-6

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