The Effects of MS-275 Derivative in Diabetic Skeletal Muscle Atrophy

Aim/hypothesis: Histone Deacetylase (HDAC) is considered one of the pathogenic factors that induced muscle atrophy. MS-275, HDAC inhibitor, plays an important role in many physiological processes, and includes muscle contraction, mitochondrial metabolism, and decision of cell fate. Recently it was reported MS275 prevented insulin resistance and obesity. However, the effects of MS-275 derivative in diabetic skeletal muscle atrophy have not been well studied. In this study, we investigated the preventive effects of MS-275 derivative in diabetic muscle atrophy using db/db mice. Method: To investigate the effects of MS-275 derivative on diabetic muscle atrophy, db/db mice were randomly divided into three groups: control group, db/db group, and db/db plus MS-275 derivative group. The mice were administered MS-275 derivative (7 mg/kg/i.p) for 4 weeks. The H&E stained sections were measured for cross-sectional area analyses using Image J software. To investigate the molecular mechanisms of MS-275 derivative, several factors related with muscle atrophy were tested using RT-PCR. Results: Administration of MS-275 derivative to db/db mice suppressed muscle weight loss and insulin resistance. As a result of examining muscle mass and fat accumulation in the hindlimb by MRI, we found MS-275 derivative reduced fat accumulation and improved muscle loss. Tibialis anterior (TA) muscle and gastrocnemius (GA) muscle had significantly induced muscle atrophy in db/db mice. However, treatment with MS-275 derivative prevented weight loss of TA and GA muscles and it also recovered reduction of muscle fiber size. Interestingly, MS-275 derivative dramatically reduced atrophy related gene expressions in TA muscle. Conclusion: In this study, MS-275 derivative ameliorated muscle atrophy through a reduction of atrophy related gene expressions in db/db mice. These results suggest MS-275 derivative may be a basis for the development of therapeutic drugs as applied to atrophy-related muscular or metabolic diseases. Disclosure N.Lee: None. H.Kim: None. T.Kim: None. S.An: None. K.Lee: None. Y.Kim: None. S.Choi: None. Y.Kim: None. Y.Son: None. S.Choi: None. Y.Y.Kang: None. J.Jeon: None. S.Han: None.