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Here, we tested the hypothesis that high intrinsic aerobic capacity and exercise both increase hepatic BA synthesis measured by the incorporation of 2H2O. We also leveraged mice with inducible liver-specific deletion of Cyp7a1 (LCyp7a1KO), which encodes the rate-limiting enzyme for BA synthesis, to test if exercise-induced BA synthesis is critical for exercise to reduce hepatic steatosis. The synthesis of hepatic BA, cholesterol, and de novo lipogenesis was measured in rats bred for either high (HCR) or low (LCR) aerobic capacity consuming acute and chronic high-fat diets. HCR rats had increased synthesis of cholesterol and certain BA species in the liver compared to LCR rats. We also found that chronic exercise with voluntary wheel running (VWR) (4 weeks) increased newly synthesized BAs of specific species in male C57BL\/6J mice compared to sedentary mice. Loss of Cyp7a1 resulted in fewer new BAs and increased liver triglycerides compared to controls after a 10-week high-fat diet. Additionally, exercise via VWR for 4 weeks effectively reduced hepatic triglycerides in the high-fat diet-fed control male and female mice as expected; however, exercise in LCyp7a1KO mice did not lower liver triglycerides in either sex. These results show that aerobic capacity and exercise increase hepatic BA metabolism, which may be critical for combatting hepatic steatosis.<\/jats:p>","DOI":"10.1093\/function\/zqaf019","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T20:12:35Z","timestamp":1744056755000},"source":"Crossref","is-referenced-by-count":3,"title":["Aerobic Capacity and Exercise Mediate Protection Against Hepatic Steatosis via Enhanced Bile Acid Metabolism"],"prefix":"10.1152","volume":"6","author":[{"given":"Benjamin A","family":"Kugler","sequence":"first","affiliation":[{"name":"Kansas Medical Center Departments of Cell Biology and Physiology, , Kansas City, KS, 66160 ,","place":["USA"]},{"name":"KU Diabetes Institute, Kansas Medical Center Division of Endocrinology and Clinical Pharmacology, Department of Internal Medicine, , Kansas City, KS, 66106 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,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Ernst","sequence":"additional","affiliation":[{"name":"Kansas Medical Center Departments of Cell Biology and Physiology, , Kansas City, KS, 66160 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Schwartze","sequence":"additional","affiliation":[{"name":"Kansas Medical Center Departments of Cell Biology and Physiology, , Kansas City, KS, 66160 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Allen","sequence":"additional","affiliation":[{"name":"Kansas Medical Center Departments of Cell Biology and Physiology, , Kansas City, KS, 66160 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiangang","family":"Li","sequence":"additional","affiliation":[{"name":"University of Oklahoma Health Sciences Center Department of Biochemistry and Physiology and Harold Hamm Diabetes Center, , Oklahoma City, OK, 73104 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A","family":"Crawford","sequence":"additional","affiliation":[{"name":"Molecular Biology, and Biophysics, University of Minnesota Division of Molecular Medicine, Department of Medicine, and Departments of Biochemistry, , Minneapolis, MN, 55455 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2019-5939","authenticated-orcid":false,"given":"Lauren G","family":"Koch","sequence":"additional","affiliation":[{"name":"The University of Toledo Department of Physiology and Pharmacology, , Toledo, OH, 43614 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven L","family":"Britton","sequence":"additional","affiliation":[{"name":"University of Michigan Department of Anesthesiology, , Ann Arbor, MI, 48109 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kartik","family":"Shankar","sequence":"additional","affiliation":[{"name":"USDA Agricultural Research Service, Responsive Agricultural Food Systems Research Unit , College Station, TX ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn C","family":"Burgess","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center Center for Human Nutrition and Department of Pharmacology, , Dallas, TX, 75390 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7920-7466","authenticated-orcid":false,"given":"John P","family":"Thyfault","sequence":"additional","affiliation":[{"name":"Kansas Medical Center Departments of Cell Biology and Physiology, , Kansas City, KS, 66160 ,","place":["USA"]},{"name":"KU Diabetes Institute, Kansas Medical Center Division of Endocrinology and Clinical 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