Mice lacking myotubularin-related protein 14 show accelerated high-fat diet-induced lipid accumulation and inflammation.
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.
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
L
Yin
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.
Peng
P
Yong-Bo
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.
Yu
Y
Meng-Fei
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.
Chen
C
Weiwei
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.
Zhao
Z
Ping
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.
Xue
X
Lu
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.
Ma
M
Li-Qun
Wuhan Youzhiyou Biopharmaceutical Co., Ltd., 666 Gaoxin Rd, Biolake, Wuhan, 430075, China.
Cai
C
Congli
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. qinghualiu95@163.com.
Liu
L
Qing-Hua
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. shenjinhua2013@163.com.
Shen
S
Jinhua
D052242:Adiponectin / Q000097:blood / Q000235:genetics / Q000378:metabolism; D000273:Adipose Tissue / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D005786:Gene Expression Regulation; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D006943:Hyperglycemia / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006949:Hyperlipidemias / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020738:Leptin / Q000097:blood / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000209:etiology / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D011897:Random Allocation; D015430:Weight Gain
D052242:Adiponectin; C499919:Adipoq protein, mouse; D016207:Cytokines; D051275:Glucose Transporter Type 4; D020738:Leptin; C495693:Slc2a4 protein, mouse; C554751:MTMR14 protein, mouse; D010744:Phosphoric Monoester Hydrolases
High-fat diet; Inflammation; MTMR14; Obesity; Phosphatase