Yin Lv, Yong-Bo Peng, Meng-Fei Yu, Weiwei Chen, Ping Zhao, Lu Xue, Li-Qun Ma, Congli Cai, Qing-Hua Liu, Jinhua Shen
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.
Wuhan Youzhiyou Biopharmaceutical Co., Ltd., 666 Gaoxin Rd, Biolake, Wuhan, 430075, China.
J Physiol Biochem. 2017 Feb;73(1):17-28. doi: 10.1007/s13105-016-0520-6. Epub 2016 Nov 2.
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.
磷酸肌醇磷酸酶，即肌管素相关蛋白14（MTMR14），据报道在调节小鼠肌肉性能、自噬和衰老过程中发挥着重要作用。我们之前发现，即使在正常饮食（NCD）条件下，MTMR14基因敲除（KO）小鼠比其野生型（WT）同窝小鼠更早体重增加，这表明该基因可能也参与调节新陈代谢。在本研究中，我们评估了MTMR14基因缺陷对高脂饮食（HFD）诱导的肥胖、脂质积累、代谢紊乱以及喂食NCD或HFD的WT和MTMR14-KO小鼠炎症反应的影响。为此，与年龄匹配的WT对照相比，喂食HFD的MTMR14-KO小鼠体重、血糖水平、血清甘油三酯（TG）水平和总胆固醇（TC）水平显著升高。此外，KO小鼠的脂质积累也增加。同时，喂食HFD的MTMR14-KO小鼠肝脏、肌肉和脂肪组织中与代谢相关基因（Glut4、脂联素和瘦素）的表达存在差异。更重要的是，相对于对照，MTMR14-KO小鼠肝脏、肌肉和脂肪组织中几种与炎症相关基因（TNF-α、IL-6、IL-1β和MCP-1）的表达显著增加。综上所述，这些结果表明MTMR14基因缺陷会加速HFD诱导的代谢功能障碍和炎症反应。此外，结果表明加剧的代谢功能障碍和炎症反应可能通过PI3K/Akt和ERK信号通路进行调节。
