High‐fat diet augments muscle atrophy by changes of muscle atrophy‐related genes in mice

Introduction Recently, it has been reported that obesity accelerates muscle atrophy and protein degradation induced by 14‐days denervation in mice. Muscle atrophy primarily results from accelerated protein degradation and is associated with increased expression of two muscle‐specific ubiquitin ligases: MuRF1 and atrogin‐1. PGC1α is the master transcription regulator that stimulates mitochondrial biogenesis, and expression level of PGC1α was reduced in obesity and muscle atrophy. However, the expression level of these genes in response to muscle atrophy on obesity is still unclear. The purpose of this study was to investigate the expression level of MuRF1, atrogin‐1 and PGC1α during muscle atrophy in mice fed a high‐fat diet. Methods This study was approved by the Juntendo University Animal Care Committee (H28‐14). Fifty‐two male C57BL/6J mice (6 weeks old) were randomly divided into two groups: 1) normal diet (ND, n=26), 2) high‐fat diet (HFD, n=26). HFD were fed a high‐fat diet (60% calories from fat) for 16 weeks, while ND received a chow diet (10% calories from fat). Following 16 weeks of each experimental diet intake, all mice were lightly anaesthetized with the inhalant isoflurane and one hindlimb was immobilized in the plantar flexion position with casting tape. After immobilization for 1, 3, and 7 days, the soleus and plantaris muscles were removed. Statistical significance was analyzed by using two‐way ( diet and time) analysis of variance (ANOVA). Statistical significant level was set at P < 0.05. Results Body weight and epididymal fat pad mass were significantly higher in the HFD group compared with the ND group. In the 7 days, the HFD significantly augmented loss of mass rate as compared with ND. The expression level of MuRF1 mRNA 3d in soleus and plantaris muscles was significantly higher in the HFD group compared with the ND group. The expression level of atrogin‐1 mRNA was significantly increased in response to immobilization, but no changes in ND and HFD. The expression level of PGC1α mRNA was significantly reduced in response to immobilization and was lower in HFD compared with ND in soleus and plantaris muscle. Conclusion HFD augments muscle atrophy by immobilization, at least in part by increasing the expression level of MuRF1 mRNA. Support or Funding Information This study was supported in part by Japan Society for the Promotion of Science KAKENHI Grant (16H07182), President's Grant for Interfaculty Collaboration, Juntendo University (Goto A: K1613, K1708) and MEXT‐Supported Program for the Strategic Research Foundation at Private Universities. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .