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Article Title

ANALYSIS OF THE TRANSCRIPTOME OF SOLEUS MUSCLE IN SARCOPENIC OBESE MICE

Abstract

Eleanor R. Schrems1, Landen W. Saling1, Breanna M. Williams1, Francielly Morena da Silva1, Regina Cabrera1, Seongkyun Lim1, Nicholas P. Greene, FACSM1, Tyrone A. Washington1

1University of Arkansas, Fayetteville, Arkansas

Sarcopenic obesity (SO) is the metabolic condition of age-related muscle mass loss combined with increased fat deposition which leads to impaired function and disability. This is a growing concern in North America as the elderly population has grown and modern medicine has increased the life expectancy of the average adult. SO alters skeletal muscle maintenance, the basal preservation of skeletal muscle mass, function, and integrity. SO is not widely studied and a better understanding of the molecular mechanisms and altered cellular signaling in play could pave the way for future treatments. PURPOSE: The purpose of this study was to evaluate the muscle transcriptome in SO muscle and to gain a deeper understanding of genes and signaling pathways altered. METHODS: 12 young and 12 aged male mice were randomly assigned a normal chow (~16% fat) or high fat diet (60% fat) at 4 weeks of age. Based on their diets, they were assigned to 1 of 4 groups: young-lean (YL), young-obese (YO), aged-lean (AL), and aged-obese (AO). At 3-4 or 21-23 months of age, soleus muscle was extracted. RNA was isolated from the soleus and sequenced. Differentially expressed genes were verified with qRT-PCR. Data were analyzed by 2-way ANOVA and post hoc analysis done using a Tukey’s multiple comparison test. RESULTS: There was interaction between age and obesity to alter body mass (p=0.005). YO mice had a 24% greater body mass than YL (p=0.002) and AO had a 35% greater body mass than AL (p<0.001). There was a main effect of age to decrease soleus muscle mass (p<0.001). There was an interaction between age and obesity to alter soleus muscle mass (P=0.023). A total of 40 genes were differentially expressed in the soleus of AL vs AO mice. Two of these genes are related to stem cell activation and magnesium regulation, these genes were selected for further analysis of mRNA abundance. There was a main effect of obesity to increase trpm6 mRNA abundance 80% (p<0.001) and a main effect of age to increase cntf mRNA abundance 11% (p =0.026). CONCLUSION: The increase of cntfindicate stem cell activation and a possible protective mechanism against muscle wasting caused during obesity. Additionally, an upregulation of trpm6 with age could indicate an increase in magnesium regulation, which may indicate a protective effect against sarcopenia.

ACKNOWLEDGEMENTS: This study was funded by the Arkansas Biological Institute.

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