Abstract
Sarcopenia, i.e., the loss of muscle mass and degradation of muscle that can occur with aging, increases an individual's risk of death. MicroRNAs are negative regulators of gene expression that have been implicated in many biological processes, including metabolism. Here we investigated the role of microRNA in sarcopenia. Orchiectomized (ORX) mice have decreased body weight and muscle mass, a smaller cross-sectional area of muscle, and impaired glucose tolerance. In our microarray analysis of the microRNA expression in skeletal muscle, the expression of miR-23b-3p in ORX mice was significantly higher than that in Sham mice; the expression in ORX mice treated with androgen was conversely lower. The overexpression of miR-23b-3p in C2C12 myotube cells significantly upregulated the expression of myosin heavy chain, protein synthesis, ATP activity, and glucose uptake. Reporter assays revealed direct post-transcriptional regulation involving miR-23b-3p and the 3'-untranslated region of PTEN mRNA. Among male subjects with type 2 diabetes, the serum miR-23b-3p levels in the subjects with sarcopenia was significantly higher compared to the levels of the subjects without sarcopenia. Our results indicate that miR-23b-3p negatively regulates the expression of PTEN in myotube cells and induces the upregulation of glucose uptake. In addition, the serum level of miR-23b-3p can be a surrogate marker of sarcopenia. Disclosure T. Okamura: None. Y. Hashimoto: Research Support; Self; Asahi Kasei Pharma. T. Osaka: None. T. Senmaru: None. M. Hamaguchi: None. M. Fukui: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Johnson & Johnson, Kyowa Hakko Kirin Co., Ltd., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; AstraZeneca, Eli Lilly and Company, Kowa Pharmaceutical Europe Co. Ltd., Kyowa Hakko Kirin Co., Ltd., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited.
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