Metabolomics Phenotypes of the Skeletal Muscle Tissues from miR-378 Transgenic Mice
Liang Na1, Song Yipeng2, Li Changyin1, Li Hu1, Jia Haixue1, Han Wanhong1, Zhao Yixia1, Tang Huiru3*, Zhang Yong1*
Skeletal muscle is the biggest metabolic organ in the body, playing an important role in regulating whole body energy homeostasis. Our group have previously reported that miR-378 can mediate systemic energy homeostasis in mice. In order to investigate the functions of miR-378 in skeletal muscle metabolism, we applied nuclear magnetic resonance (NMR) technology to systemically study the metabolomic difference of the skeletal muscle from miR-378 transgenic (Tg) mice and its wild type (Wt) littermates. Our results demonstrate that miR-378 plays pivotal roles in regulating skeletal muscle metabolism. The content of creatine, amino acid species (glutamine, glutamate) and nucleic acid metabolic products (inosine) are significantly increased in the skeletal muscle of miR-378 Tg mice compared to its Wt littermates, whereas the content of lactate, phosphocreatine (PCr) and glycerol are significantly decreased in miR-378 Tg mice. This suggests energy deficiency in skeletal muscle of miR-378 Tg mice. We further examined possible activation of AMPK signaling pathway. Our result demonstrates the phosphorylated form of AMPK and ACC (pAMPKa and pACC) are remarkably increased in skeletal muscle of miR-378 Tg mice. The activation of AMPKa further supports the result that the overexpression of miR-378 leads to energy deficiency in skeletal muscle. Together, we provide experimental data to support the notion that miR-378 plays important role in regulating skeletal muscle metabolism.
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