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Abstract
BackgroundMyotubularin-related protein 14 (MTMR14) is a novel phosphoinositide phosphatase with roles in the maintenance of normal muscle performance, autophagy, and aging in mice. Our initial pilot study demonstrated that MTMR14 knock out (KO) mice gain weight earlier than their wild-type (WT) littermates, which suggests that this gene may also be involved in metabolism regulation.ResultsThe present study evaluated the role of MTMR14 in the development of aging-associated obesity. We found that aged MTMR14 KO mice fed a normal chow diet exhibited increased serum triglyceride, total cholesterol, and glucose levels compared to age-matched WT controls. Lipid accumulation was also increased in aged KO mice. Several inflammatory cytokines and adipokines were dramatically dysregulated in the metabolic tissues of aged MTMR14 KO mice compared to control mice. Circulating inflammatory cytokines were significantly elevated and plasma adipokine levels were abnormally regulated in aged MTMR14 KO mice. These data suggest that MTMR14 deficiency caused a late-onset inflammation and metabolic dysfunction. Further study demonstrated that this exacerbated metabolic dysfunction and inflammation may be regulated by the phosphoinositide 3 kinase/protein kinase B and extracellular signal-regulated protein kinase signaling pathways.ConclusionsOur current research suggests that MTMR14 deletion induces overweight and adult obesity accompanied by chronic inflammation in an age-dependent manner.
Highlights
Myotubularin-related protein 14 (MTMR14) is a novel phosphoinositide phosphatase with roles in the maintenance of normal muscle performance, autophagy, and aging in mice
Our recent work revealed that myotubularin-related protein 14 (MTMR14) knock out (KO) mice weighed more than their WT littermates as adults, especially aged mice, which suggests that MTMR14 is involved in the regulation of body weight and metabolism
MTMR14 KO mice got fat earlier than WT mice Our previous results demonstrated that MTMR14 KO mice were born at the expected Mendelian ratio and did not exhibit obvious abnormalities [14]
Summary
Myotubularin-related protein 14 (MTMR14) is a novel phosphoinositide phosphatase with roles in the maintenance of normal muscle performance, autophagy, and aging in mice. Our initial pilot study demonstrated that MTMR14 knock out (KO) mice gain weight earlier than their wild-type (WT) littermates, which suggests that this gene may be involved in metabolism regulation. Obesity is Myotubularin-related protein 14 is a novel phosphoinositide phosphatase. MTMR14 is involved in the regulation of autophagy and aging [15,16,17,18,19]. Our recent work revealed that MTMR14 KO mice weighed more than their WT littermates as adults, especially aged mice, which suggests that MTMR14 is involved in the regulation of body weight and metabolism
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