(OR36-02-24) The Impact of a High-Fat Diet Coupled With Diverse Aerobic Exercise on the Murine Skeletal Muscle Transcriptome

Objectives: Eating a high-fat diet (HFD) and leading a sedentary lifestyle result in obesity and many health issues. Exercise counters many adverse health effects of a HFD and associated obesity. However, the complex molecular changes that occur in skeletal muscle in response to exercising while consuming a HFD are not yet known. We investigated the interplay between diverse exercise regimes and consuming a HFD on transcriptomics and metabolomics of skeletal muscle tissue.

Methods: Mice were randomized into six groups – two sedentary control groups and four exercise groups (unrestricted access or access restricted to 75%, 50%, or 25% of unrestricted running). Mice in sedentary control groups were fed either an AIN93G diet or a HFD (HFD-C). The mice assigned to the four exercise groups were fed with the HFD. Total RNA was extracted from flash frozen gastrocnemius muscle samples for RNA sequencing and transcriptome analyses. A part of the same frozen samples was used for metabolome analyses.

Results: A total of 12053 transcripts were differentially expressed in the exercise groups compared to the HFD-C. When comparing the HFD-C and the different exercise groups, exercising at 50% of unrestricted access (HF-50UnR) resulted in maximum differentially expressed transcripts. Genes down regulated in HF-50UnR group were mostly associated with MAPK and cAMP signaling pathways, whereas up-regulated genes were associated with PPAR and JAK-STAT signaling pathways, along with tryptophane and nitrogen metabolism. The metabolites glycine, glutathione, 1.5-anhydroglucitol, and aminomalonic acid were downregulated in all exercise groups compared to the control groups. Consistent with these findings, the transcripts correlated to the expression of these metabolites were also altered.

Conclusions: This study provides a detailed characterization of skeletal muscle transcriptome and metabolome networks critical in determining the beneficial effects of exercise in the context of obesity and associated disease management. These results suggest that a moderate amount of exercise may be more efficient at offsetting the detrimental effects of consuming a HFD.

Funding Sources: US Department of Agriculture, Agricultural Research Service #3062-51000-057-000D and 3062-51000-056-00D