PRELIMINARY STUDY: MUSCLE WASTING IS EXACERBATED IN APCMin/+ MICE WITH LEUCINE SUPPLEMENTATION
Katarina A. Bejarano1, Wesley S. Haynie1, Richard, A. Perry1, Lemuel A. Brown1, David E. Lee1, Jacob L. Brown1, Megan E. Rosa-Caldwell1, Nicholas P. Greene1, Tyrone A. Washington1. 1University of Arkansas, Fayetteville, Arkansas.
Cancer Cachexia is a devastating syndrome that affects around 50-80% of cancer patients and is characterized by a rapid, drastic fat and muscle mass loss. The APCMin/+ mouse strain is a well-studied mouse model of human colorectal cancer and cancer cachexia. The branched-chain amino acid leucine is known to stimulate muscle growth/maintenance through activation of the protein mTOR and protein synthesis. PURPOSE: To examine the effects of chronic leucine supplementation on the development of cancer cachexia in APCMin/+ mice. METHODS: 7 APCMin/+ mice (APC) and 11 wild-type (WT) were used for this study. The animals were assigned to the following groups: WT no leucine (WTNL, n=5), WT leucine (WTL, n=5), APCMin/+ no leucine (APCNL, n=5) and APCMin/+ leucine (APCL, n=2). Mice were given ad libitum access to food and water. Mice in the leucine groups received leucine in their water at a concentration of 1.5%. Plantaris muscles and tibias were excised at 20 weeks of age. Tissue was immediately frozen for morphology and gene expression analysis using RT-qPCR. RESULTS: The number of polyps increased in APCMin/+ compared to WT (46.57 ± 2.44 vs 0.00 ± 0.00). The number of polyps < 1 mm was increased (7.75 ± 2.05 vs. 14.33 ± 1.45) in APCL compared to APCNL (p<.05). There was a main effect for APCMin/+ to have lower body mass in than WT mice (p<.0001). There was a main effect of genotype to decrease plantaris weight/tibia length in APCMin/+ mice (p<.0001) and a main effect of leucine to decrease plantaris weight/tibia length in APCMin/+ mice compared to WT mice (p<.05). There was an ~8-fold increase in atrogin-1 gene expression in APCNL compared to WTNL mice (p<.05). Atrogin-1 gene expression was ~7-fold lower in APCL compared to APCNL (p<.05). There was a main effect of genotype to increase MuRF1 expression in APCMin/+ mice compared to WT mice (p<.05). There was a main effect of leucine to decrease MuRF1 expression in APCMin/+ mice compared to WT mice (p<.05). CONCLUSION: Contrary to our initial hypothesis, leucine supplementation seemed to exacerbate muscle mass loss in cachectic mice. Based on gene expression of the E3 ubiquitin ligases, this loss in muscle mass may be independent of protein degradation.
Bejarano, KA; Haynie, WS; Perry, RA; Brown, LA; Lee, DE; Brown, JL; Rosa-Caldwell, ME; Greene, NP; and Washington, TA
"PRELIMINARY STUDY: MUSCLE WASTING IS EXACERBATED IN APCMin/+ MICE WITH LEUCINE SUPPLEMENTATION,"
International Journal of Exercise Science: Conference Proceedings: Vol. 11:
6, Article 9.
Available at: https://digitalcommons.wku.edu/ijesab/vol11/iss6/9