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We have developed a model of MASLD due to the loss of hepatocyte peroxisome proliferator-activated receptor \u03b1 (PPAR\u03b1HEPKO). We found that plasma beta-hydroxybutyrate (BHOB) levels were significantly reduced in PPAR\u03b1HEPKO mice and aimed to investigate the therapeutic potential of restoring BHOB levels in the development of CVD in these mice. Thirty-week-old PPAR\u03b1HEPKO and control PPAR\u03b1FL\/FL mice were randomized to receive 1,3 butanediol (1,3-BDO), a precursor of BHOB, in drinking water for 6 weeks. 1,3-BDO treatment resulted in a significant increase in plasma BHOB levels, a significant decrease in mean arterial blood pressure, improvement in systolic and diastolic function, a decrease in vascular stiffness, and improved exercise performance in PPAR\u03b1HEPKO mice. 1,3-BDO treatment did not alleviate hepatic steatosis in PPAR\u03b1HEPKO mice; however, it improved plasma cholesterol levels and decreased cardiac lipid accumulation, fibrosis, and apoptosis. 1,3-BDO treatment also resulted in a significant increase in cardiac AMP-activated protein kinase (AMPK) levels. Increasing plasma BHOB levels reverses CVD in our mouse model of MASLD. A similar approach could be an effective strategy for preventing the development of CVD in patients with human MASLD.<\/jats:p>","DOI":"10.3390\/ijms27125354","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T08:57:58Z","timestamp":1781513878000},"page":"5354","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cardioprotective Effects of 1,3 Butanediol in MASLD via Reversal of Cardiac Lipid Accumulation and Suppression of Cardiac Fibrosis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1020-2170","authenticated-orcid":false,"given":"Olufunto O.","family":"Badmus","sequence":"first","affiliation":[{"name":"Department of Physiology & Biophysics, Cardiovascular-Renal Research Center, Cardiorenal, and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4374-4354","authenticated-orcid":false,"given":"Landon D.","family":"Parrow","sequence":"additional","affiliation":[{"name":"Department of Physiology & Biophysics, Cardiovascular-Renal Research Center, Cardiorenal, and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karis E.","family":"McGowen","sequence":"additional","affiliation":[{"name":"Department of Physiology & Biophysics, Cardiovascular-Renal Research Center, Cardiorenal, and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LaBrenda","family":"Bell","sequence":"additional","affiliation":[{"name":"Department of Physiology & Biophysics, Cardiovascular-Renal Research Center, Cardiorenal, and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0924-7689","authenticated-orcid":false,"given":"Jennifer R.","family":"Greer","sequence":"additional","affiliation":[{"name":"Department of Physiology & Biophysics, Cardiovascular-Renal Research Center, Cardiorenal, and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela de Carvalho","family":"Cruz","sequence":"additional","affiliation":[{"name":"Department of Physiology & Biophysics, Cardiovascular-Renal Research Center, Cardiorenal, and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7599-1529","authenticated-orcid":false,"suffix":"Jr.","given":"Terry D.","family":"Hinds","sequence":"additional","affiliation":[{"name":"Drug & Disease Discovery D3 Research Center, Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8359-4008","authenticated-orcid":false,"given":"David E.","family":"Stec","sequence":"additional","affiliation":[{"name":"Department of Physiology & Biophysics, Cardiovascular-Renal Research Center, Cardiorenal, and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1097\/MD.0b013e3182779d49","article-title":"Nonalcoholic fatty liver disease in lean individuals in the United States","volume":"91","author":"Younossi","year":"2012","journal-title":"Medicine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.jhepr.2019.08.002","article-title":"Non-alcoholic fatty liver disease in lean individuals","volume":"1","author":"Albhaisi","year":"2019","journal-title":"JHEP Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3212","DOI":"10.1111\/jgh.15597","article-title":"Visceral adiposity as a risk factor for lean non-alcoholic fatty liver disease in potential living liver donors","volume":"36","author":"Lee","year":"2021","journal-title":"J. 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