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Mice lacking myotubularin-related protein 14 show accelerated high-fat diet-induced lipid accumulation and
Lv Yin1, Peng Yong-Bo1, Yu Meng-Fei1
1Institute 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.
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.
Insights
Myotubularin-related protein 14 (MTMR14) deficiency exacerbates high-fat diet-induced obesity and inflammation in mice. MTMR14 loss accelerates metabolic dysfunction, potentially through PI3K/Akt and ERK signaling pathways.
Area of Science:
- Metabolic research
- Molecular biology
- Obesity research
Background:
- Myotubularin-related protein 14 (MTMR14) is a phosphoinositide phosphatase involved in muscle performance, autophagy, and aging.
- Previous studies indicated MTMR14-knockout (KO) mice exhibit earlier weight gain on normal diets.
- This suggests a potential role for MTMR14 in metabolic regulation.
Purpose of the Study:
- To investigate the impact of MTMR14 deficiency on high-fat diet (HFD)-induced obesity.
- To assess effects on lipid accumulation, metabolic disorders, and inflammation in MTMR14-KO mice.
- To explore the underlying signaling pathways involved.
Main Methods:
- Comparison of wild-type (WT) and MTMR14-KO mice fed normal chow diet (NCD) or HFD.
- Measurement of body weight, blood glucose, serum triglyceride (TG), and total cholesterol (TC).
- Analysis of metabolism and inflammation-associated gene expression in liver, muscle, and adipose tissue.
- Investigation of PI3K/Akt and ERK signaling pathways.
Main Results:
- MTMR14-KO mice on HFD showed significantly increased body weight, blood glucose, TG, and TC levels compared to WT controls.
- Increased lipid accumulation was observed in KO mice.
- Expression of metabolism-related genes (Glut4, adiponectin, leptin) and inflammation markers (TNF-α, IL-6, IL-1β, MCP-1) was altered in KO mice, particularly in the liver, muscle, and adipose tissue.
- Exacerbated metabolic dysfunction and inflammation were linked to PI3K/Akt and ERK signaling.
Conclusions:
- MTMR14 deficiency accelerates HFD-induced obesity, metabolic dysfunction, and inflammation.
- Altered lipid metabolism and increased inflammatory responses are key consequences of MTMR14 loss.
- The PI3K/Akt and ERK signaling pathways appear to mediate the effects of MTMR14 deficiency on metabolic health and inflammation.
