Effects of defined voluntary running distances coupled with high-fat diet consumption on the murine skeletal muscle transcriptome

Exercise counters many adverse health effects of consuming a high-fat diet (HFD). 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 HFD consumption for 12 weeks on the adaptation of the skeletal muscle transcriptome. C57BL/6 male mice were randomized into six groups – two sedentary control groups and four exercise groups. An unrestricted running group that averaged 8.3 km/day and exercise groups that were restricted to 75%, 50%, or 25% of unrestricted running that averaged 6.3, 4.2, and 2.1 km/day, respectively. Control groups were fed either an AIN93G diet or a HFD (HFD-C) and the exercise groups were fed the HFD. Total RNA was extracted from flash frozen gastrocnemius muscle for sequencing and transcriptome analyses. 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 (HFD-50%) resulted in maximum differentially expressed transcripts. Genes down regulated in HFD-50% 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 tryptophan and nitrogen metabolism. These results demonstrate that running distance has a significant impact on the adaptation of the skeletal muscle transcriptome to exercise. Furthermore, transcriptome adaptations were more prominent in response to middle-distance running.