Madeline G. Amos1, Megan E. Rosa-Caldwell1, Wesley S. Haynie1, Kirsten R. Dunlap1, Seongkyun Lim1, Lisa T. Jansen1, Jacob L. Brown1, David E. Lee1, TyroneA.Washington1, Michael P. Wiggs2, Nicholas P. Greene, FACSM11University of Arkansas, Fayetteville, AR; 2University of Texas at Tyler, Tyler, TX

Muscle loss is an important predictor of morbidity and mortality across a variety of diseases. Males and females appear to differ on clinical outcomes in relation to disuse-induced muscle loss, however reasons for these different responses have not been investigated. PURPOSE: To investigate measures of muscle oxidative metabolism during the time-course of disuse-induced atrophy in male and female mice. METHODS: Disuse atrophy was induced using hindlimb unloading in50male and 50 female mice for 0 (CON), 1, 2, 3,or 7 days(n=~10/group). Muscle sections of the tibialis anterior were stained for succinate dehydrogenase (SDH,a measure of oxidative metabolism) and cross sectional area(CSA).CSAby SDH staining was used to investigate the effect of disuse on different muscle fiber phenotypes. mRNA content of Pparawas measured in the gastrocnemius, soleus, and extensor digitorum longus(EDL)muscles. Data were analyzed within each sex by one way ANOVA and trend analysis with p<0.05 indicating statistical significance. RESULTS: CSA of SDH positive fibers progressively decreased in both male and female mice. CON animals (male and female) had SDH positive fiber CSA of ~400 μm2and 7 day unloaded animals had CSAs of ~300 μm2.Both male and female mice had an SDH negative CSA of ~650 μm2, with no significant differences in fiber CSA noted across groups. In the gastrocnemius muscle, Ppara content was ~50-60% lower at 1 day of unloading in males and females and remained depressed in all experimental groups. In soleus muscles of females, Ppara was ~60% lower at days 1, 2, and 3 compared to CON, but then recovered back to CON levels. Whereas in males, Pparawas ~60% lower with 1 day of unloading and remained depressed in 1, 2, 3, and 7 day groups. In females ,there were no differences in Ppara content in EDL across all groups. In males, there was ~50-75% lower Ppara in EDL content that reached statistical significance at 2 days unloading and remained depressed throughout intervention groups. CONCLUSION: Disuse results in muscle loss in both male and females and appears to result in similar alterations to oxidative metabolism across multiple tissues. Future studies should investigate if improving oxidative metabolism is protective against disuse atrophy in males and females.

ACKNOWLEDGEMENTS: This study was funded by the National Institutes of Health, Award number: R15 AR069913/AR/NIAMS

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