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However, 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 on the adaptation of skeletal muscle transcriptome. C57BL\/6 male mice were randomized into five groups\u2014one sedentary control group and four exercise groups. The exercise groups consisted of an unrestricted running group (8.3\u2009km\/day) and three groups that were restricted to 75%, 50%, or 25% of unrestricted running (6.3, 4.2, and 2.1\u2009km\/day, respectively). Total RNA was extracted from frozen gastrocnemius muscle for transcriptome analyses. DEG counts were 1347, 1823, 1103, and 1107 and there were 107, 169, 67, and 89 unique genes present in the HFD\u201025%, HFD\u201050%, HFD\u201075%, and HFD\u2010U, respectively. Comparing exercise groups, we found that exercising at 50% resulted in the most differentially expressed transcripts with the MAPK and PPAR signaling pathways enriched in down\u2010 and up\u2010regulated genes, respectively. These results demonstrate that running distance impacts the adaptation of the skeletal muscle transcriptome to exercise and suggest that middle\u2010distance running may provide the greatest protection against high\u2010fat diet\u2010induced stress coupled with exercise.<\/jats:p>","DOI":"10.14814\/phy2.70170","type":"journal-article","created":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T02:36:59Z","timestamp":1737081419000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of defined voluntary running distances coupled with high\u2010fat diet consumption on the skeletal muscle transcriptome of male mice"],"prefix":"10.14814","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1633-207X","authenticated-orcid":false,"given":"Afrina","family":"Brishti","sequence":"first","affiliation":[{"name":"United States Department of Agriculture, Agricultural Research Service Grand Forks Human Nutrition Research Center  Grand Forks North Dakota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J.","family":"Johnson","sequence":"additional","affiliation":[{"name":"United States Department of Agriculture, Agricultural Research Service Grand Forks Human Nutrition Research Center  Grand Forks North Dakota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel G.","family":"Palmer","sequence":"additional","affiliation":[{"name":"United States Department of Agriculture, Agricultural Research Service Grand Forks Human Nutrition Research Center  Grand Forks North Dakota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Obayed","family":"Raihan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Health Sciences and Pharmacy Chicago State University  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Yan","sequence":"additional","affiliation":[{"name":"United States Department of Agriculture, Agricultural Research Service Grand Forks Human Nutrition Research Center  Grand Forks North Dakota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6954-9523","authenticated-orcid":false,"given":"Shanon L.","family":"Casperson","sequence":"additional","affiliation":[{"name":"United States Department of Agriculture, Agricultural Research Service Grand Forks Human Nutrition Research Center  Grand Forks North Dakota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,16]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.07.051"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2022.2063006"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01783-y"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10040537"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.2337\/db19-1218"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01153-1"},{"key":"e_1_2_11_8_1","article-title":"Assessment of murine exercise endurance without the use of a shock grid: an alternative to forced exercise","volume":"90","author":"Conner J. 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