Location: Healthy Body Weight Research
Title: Effects of defined voluntary running distances coupled with high-fat diet consumption on the murine skeletal muscle transcriptomeAuthor
![]() |
BRISHTI, AFRINA - Oak Ridge Institute For Science And Education (ORISE) |
![]() |
JOHNSON, SARAH - Former ARS Employee |
![]() |
PALMER, DANIEL - University Of North Dakota |
![]() |
RAIHAN, MD OBAYED - Chicago State University |
![]() |
Yan, Lin |
![]() |
Casperson, Shanon |
Submitted to: Physiological Reports
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 12/16/2024 Publication Date: 1/16/2025 Citation: Brishti, A., Johnson, S., Palmer, D.G., Raihan, M., Yan, L., Casperson, S.L. 2025. Effects of defined voluntary running distances coupled with high-fat diet consumption on the murine skeletal muscle transcriptome. Physiological Reports. 13(2):Article e70170. https://doi.org/10.14814/phy2.70170. DOI: https://doi.org/10.14814/phy2.70170 Interpretive Summary: A significant percentage of Americans regularly eat a high-fat diet, which is associated with excess body fat and numerous health issues. Research has shown that exercise helps to overcome those adverse health conditions. So, we investigated how the combination of eating a high-fat diet while doing daily aerobic exercise at defined running distances influences skeletal muscle gene expression. This was done in a rodent model using C57BL/6 (wild type) male mice. The mice were randomly divided into six groups – two sedentary control groups and four exercise groups. An unrestricted running group that averaged 8.3 km/day and 3 exercise groups that were limited to 75%, 50%, or 25% of the distance ran by the unrestricted group. The running distance for these groups averaged 6.3, 4.2, and 2.1 km/day, respectively. The two sedentary control groups were fed either a normal fat diet or a high-fat diet and the four exercise groups were fed the high-fat diet. Total RNA was extracted from the gastrocnemius muscle for sequencing and genomic analyses. Gastrocnemius muscle is the chief muscle of the calf of the leg, which flexes the knee and foot. A total of 12053 genes were differentially expressed in the exercise groups compared to the high-fat diet fed control group. When we compared this group with the four different exercise groups separately, we found that exercising at 50% of the unlimited running group resulted in the most differentially expressed genes. These results show that running distance significantly influences how the skeletal muscle adapts to varying amounts of aerobic exercise. Technical Abstract: 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. The exercise groups consisted of an unrestricted running group that averaged 8.3 km/day and three 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 1094 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 the most differentially expressed transcripts. Genes down-regulated in HFD-50% group were mostly associated with MAPK and cAMP signaling pathways, whereas up-regulated genes were mostly 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. |