Role of irisin in androgen-deficient muscle wasting and osteopenia in mice
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Androgen deficiency plays a crucial role in the pathogenesis of male osteoporosis and sarcopenia. Myokines have recently been identified as humoral factors that are involved in the interactions between muscle and bone; however, the influence of androgen deficiency on these interactions remains unclear. Therefore, we herein investigated the roles of humoral factors linking muscle to bone using orchidectomized mice with sarcopenia and osteopenia. Orchidectomy (ORX) significantly reduced muscle mass, grip strength, and trabecular bone mineral density (BMD) in mice. Among the myokines examined, ORX only significantly reduced fibronectin type III domain-containing 5 (Fndc5) mRNA levels in both the soleus and gastrocnemius muscles of mice. In simple regression analyses, Fndc5 mRNA levels in the soleus muscle positively correlated with trabecular BMD, but not cortical BMD. The administration of irisin, a product of Fndc5, significantly protected against the decrease induced in trabecular BMD, but not muscle mass, by androgen deficiency in mice. In conclusion, the present results demonstrated that androgen deficiency decreases the expression of irisin in the skeletal muscle of mice. Irisin may be involved in muscle/bone relationships negatively affected by androgen deficiency.
KeywordsAndrogen deficiency Irisin Muscle wasting Osteopenia
This study was partly supported by a Grant from Takeda Science Foundation and a Grant from Mitsui Life Social Welfare Foundation to N.K., a grant from Kindai Research Enhancement Grant (21st Century Joint Research Enhancement Grant) to H.K., Grants-in-Aid for Scientific Research (C:15K08220) to H.K. and (C:16K08534) to N.K., and a Grant-in-Aid for Scientific Research on Innovative Areas (Grant number 15H05935, “Living in Space”) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan to H.K.
SI, NK, and HK contributed to the conception and design of the research. SI, NK, and KO performed the experiments. SI and NK analyzed the data. SI, NK, MA, and HK interpreted the results of the experiments. SI and NK prepared the figures. SI drafted the manuscript. SI, NK, and HK edited and revised the manuscript. All authors approved the final version of the manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare no conflicts of interest.
The study was conducted with the approval of the Experimental Animal Welfare Committee of Kindai University (Permit number: KAME-28-016). All experimental procedures were performed according to the guidelines of the National Institutes of Health and the institutional rules for the use and care of laboratory animals at Kindai University.
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