GROWTH DIFFERENTIATION FACTOR 5 IS A PARACRINE REGULATOR IN SARCOPENIC OBESITY
Landen W. Saling1, Eleanor R. Schrems1, Seongkyun Lim1, Francielly Morena da Silva1, Ana Regina Cabrera1, Kevin A. Murach1, Nicholas P. Greene1, FACSM, Tyrone A. Washington1
1University of Arkansas, Fayetteville, Arkansas
Sarcopenic obesity (SO) differentiates itself from sarcopenia and obesity by exhibiting a more detrimental and complex condition that increases the risk of mortality. Sarcopenic obese individuals suffer from greater physical disability and muscle weakness than sarcopenic and obese individuals alone. In addition, altered cellular signaling that regulates increased muscle loss in SO is largely unknown. Identifying key differentially expressed genes in SO muscle are important for future investigation and the creation of therapeutics and strategies aimed at attenuating or preventing muscle loss. PURPOSE: To examine global gene expression in muscle of SO mice to determine differentially expressed (DE) genes. METHODS: After weaning, twenty-four mice were randomly assigned to young (3-4 months old) or aged (22-24 months old) groups and then randomly assigned to either a high-fat (HFD, 60% fat) or normal chow (NC, 14% fat) diet. RNA was isolated from the plantaris muscle and Next Generation RNA sequencing was conducted to determine DE genes among experimental groups. Log2 Fold Change (Log2FC) ≥ 0.6, Log2FC ≤ -0.6 and p ≤ 0.05 were the criteria used to determine significant DE genes. Real-Time Polymerase Chain Reaction was used to confirm mRNA abundance of DE genes. RESULTS: Aged-HFD mice had an ̴ 39-49% (p ≤ 0.05) reduction in plantaris to body mass ratio compared to all other groups. CYP1A1, RAB15, and CDH22 showed significant main effects (p ≤ 0.05) for diet. Age and diet interacted to alter SMOX and GDF5 mRNA abundance. There was a ̴ 26-fold increase (p ≤ 0.05) in GDF-5 mRNA abundance in the aged-HFD mice compared to all other groups. CONCLUSION: GDF-5 is associated with TGF-β and SMAD signaling. The increased GDF-5 mRNA abundance seen in SO mice could be promoting increased collagen deposition within skeletal muscle affecting muscle function. These findings show that GDF5 may play a key role in altered cellular signaling and muscle atrophy in SO muscle.
ACKNOWLEDGEMENTS: This study was funded by the Arkansas Bioscience Institute, the major research component of the Arkansas Tobacco Settlement Proceeds Act of 2000.
Saling, LW; Schrems, ER; Lim, S; da Silva, FM; Cabrera, AR; Murach, KA; Greene, FACSM, NP; and Washington, TA
"GROWTH DIFFERENTIATION FACTOR 5 IS A PARACRINE REGULATOR IN SARCOPENIC OBESITY,"
International Journal of Exercise Science: Conference Proceedings: Vol. 11:
9, Article 47.
Available at: https://digitalcommons.wku.edu/ijesab/vol11/iss9/47