{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T15:55:42Z","timestamp":1766159742772,"version":"build-2065373602"},"reference-count":52,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006481","name":"Cotton","doi-asserted-by":"publisher","award":["19\u2010056"],"award-info":[{"award-number":["19\u2010056"]}],"id":[{"id":"10.13039\/100006481","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000199","name":"U.S. Department of Agriculture","doi-asserted-by":"publisher","award":["2022\u201067013\u201036917","6054\u201041000\u2010113\u2010000 D"],"award-info":[{"award-number":["2022\u201067013\u201036917","6054\u201041000\u2010113\u2010000 D"]}],"id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Cottonseed oil (CSO) is a seed oil with a unique fatty acid composition and the ability to reduce lipid levels in humans and mice. The present study aimed to characterize the effects of dihydrosterculic acid (DHSA), a cyclopropyl fatty acid found in CSO, on lipid metabolism. First, male wild\u2010type mice were fed CSO\u2010 or isocaloric oil\u2010enriched diets (lacking DHSA) for 6\u00a0weeks. Tissues were analyzed via RNA\u2010sequencing which identified 45 differentially expressed genes within the CSO group, the majority of which are associated with lipid metabolic processes. Despite being a moderate\u2010fat diet, no changes in hepatic or plasma triglyceride were observed in the CSO group. Confirmational tissue analysis showed an increase in hepatic peroxisome proliferator\u2010activated receptor alpha (PPAR\u03b1) and PPAR\u03b1 target gene expression in the CSO group compared to control groups, suggesting that DHSA effects may be mediated through increased PPAR\u03b1 transcriptional activity and fatty acid oxidation (FAO). To test this hypothesis, female PPAR\u03b1 knockout mice were fed a CSO\u2010enriched diet. In the absence of PPAR\u03b1, the lipid\u2010lowering effect of the CSO diet was lost. Next, FAO was assessed in DHSA\u2010treated HepG2 cells by measuring mitochondrial respiration with long\u2010chain fatty acids and adenosine diphosphate substrates. Compared to the control, DHSA\u2010treated cells demonstrated a higher capacity to utilize FAO for energy production. Lastly, CSO\u2010fed mice exhibited significantly lower respiratory exchange ratio with an elevated energy expenditure (EE) compared to SFO\u2010fed mice. In total, these data suggest that the effects of CSO are the result of a DHSA\u2010dependent increase in EE via PPAR\u03b1 induction of FAO pathways.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp70033-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Previous studies with cottonseed oil\u2010 (CSO) enriched diets showed reductions in hepatic and plasma lipids; however, it is unclear whether linoleic acid or dihydrosterculic acid (DHSA), a cyclopropyl fatty acid found in CSO, is responsible for these phenotypic changes.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This study utilized a unique diet design in which mice were fed either a CSO\u2010enriched diet (DHSA\u00a0+\u00a0linoleic acid) or an isocaloric oil\u2010enriched diet (containing linoleic acid but lacking DHSA).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>RNA\u2010sequencing analysis indicated CSO\u2010fed mice demonstrated increased expression of genes associated with fatty acid oxidation (FAO) in addition to increases in the transcription factor and FAO regulator peroxisome proliferator\u2010activated receptor alpha (PPAR\u03b1) and its oxidative target genes.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Knockout of PPAR\u03b1 confirmed this transcription factor is required for the lipid\u2010lowering phenotype seen following CSO\u2010enriched diets.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>CSO\u2010fed mice demonstrated significantly lower respiratory exchange ratio and higher energy expenditure compared to chow\u2010 and SFO\u2010fed mice, indicative of elevated FAO exclusive to the CSO group.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp287121","type":"journal-article","created":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T01:20:25Z","timestamp":1755912025000},"page":"5415-5435","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dihydrosterculic acid induces hepatic PPAR\u03b1 target gene expression in mice"],"prefix":"10.1113","volume":"603","author":[{"given":"Leah S.","family":"Halls","sequence":"first","affiliation":[{"name":"Department of Nutritional Sciences University of Georgia  Athens GA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yura","family":"Son","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences University of Georgia  Athens GA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W. 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