MITOCHONDRIAL HEALTHDURING THE DEVELOPMENT OF CANCER CACHEXIA IN FEMALE MICE

Lauren C. Westervelt1, Seongkyun Lim1, Megan E. Rosa-Caldwell1, Wesley S. Haynie1, Kirsten R. Dunlap1, Lisa T. Jansen1, Michael P. Wiggs2, Tyrone A. Washington1, Nicholas P. Greene, FACSM1 1University of Arkansas, Fayetteville, AR; 2University of Texas at Tyler, Tyler, TX Cancer-cachexia is a debilitating syndrome characterized by weight loss, anemia, and wasting of adipose tissue and skeletal muscle. Muscle mass in both males and females is a strong predictor of quality of life and morbidity during cancer treatment. Mitochondrial dysfunction during cachexia has been well described in males, specifically our laboratory has found mitochondrial deteriorations to precede muscle loss in male models of cancer-cachexia. However, if these aberrations are conserved between sexes has yet to be investigated. PURPOSE: The purpose of this study was to investigate muscle mitochondrial health during cancer-cachexia development in female mice. METHODS:40 femaleC57BL/6Jmice were implanted with ~1X106Lewis Lung Carcinoma (LLC) cells into the right hind flank. Tumors were allowed to develop up to 4 weeks. After3-4 weeks of tumor development, a clear dichotomy was noted in tumor burden. As such, tumor injected females were divided into high tumor (HT, tumor size\u3e 2000mg) and low tumor groups (LT, tumor sizeRESULTS: Tibialis anterior muscle masses were ~4mg (~10%) lower in HT compared to LT and CON. Similarly, plantaris muscle masses were ~1.5mg (~11%) lower in HT compared to LT and CON. Finally, gastrocnemius masses were ~4 mg (~5%) lower in HT compared to LT and CON animals. LT and CON animals showed no differences in muscle weights. Analysis of pMitoTimer demonstrated no differences between groups. CONCLUSION:LT had negligible muscle wasting when compared to HT, these differences in muscle loss did not appear to correspond to alterations in mitochondrial health. This directly contrasts prior literature in male models of cachexia suggesting divergent mechanisms between males and females in the development of cachexia. As such, further examination of why females had a dichotomy in tumor development and subsequent wasting mechanisms are necessary in order to further understand mechanisms contributing to development of cachexia. ACKNOWLEDGEMENTS: This study was funded by the National Institutes of Health, Award Number: R15 AR069913/AR/NIAMS