Cardioprotective Effects of 1,3 Butanediol in MASLD via Reversal of Cardiac Lipid Accumulation and Suppression of Cardiac Fibrosis

Authors

• Olufunto O. Badmus, University of Mississippi School of MedicineFollow
• Landon D. Parrow, University of Mississippi School of MedicineFollow
• Karis E. McGowen, University of Mississippi School of MedicineFollow
• La Brenda Bell, University of Mississippi School of MedicineFollow
• Jennifer R. Greer, University of Mississippi School of MedicineFollow
• Marcela de Carvalho Cruz, University of Mississippi School of MedicineFollow
• Terry D. Hinds, University of KentuckyFollow
• David E. Stec, University of Mississippi School of MedicineFollow

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly associated with the development of cardiovascular disease (CVD); however, the mechanisms responsible are currently unknown. We have developed a model of MASLD due to the loss of hepatocyte peroxisome proliferator-activated receptor α (PPARα^HEPKO). We found that plasma beta-hydroxybutyrate (BHOB) levels were significantly reduced in PPARα^HEPKO mice and aimed to investigate the therapeutic potential of restoring BHOB levels in the development of CVD in these mice. Thirty-week-old PPARα^HEPKO and control PPARα^FL/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 PPARα^HEPKO mice. 1,3-BDO treatment did not alleviate hepatic steatosis in PPARα^HEPKO 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.

Document Type

Article

Publication Date

6-1-2026

Notes/Citation Information

Publisher Copyright: © 2026 by the authors.

Digital Object Identifier (DOI)

10.3390/ijms27125354

Archival?

Archival

Repository Citation

Badmus, Olufunto O.; Parrow, Landon D.; McGowen, Karis E.; Bell, La Brenda; Greer, Jennifer R.; Cruz, Marcela de Carvalho; Hinds, Terry D.; and Stec, David E., "Cardioprotective Effects of 1,3 Butanediol in MASLD via Reversal of Cardiac Lipid Accumulation and Suppression of Cardiac Fibrosis" (2026). Markey Cancer Center Faculty Publications. 509.
https://uknowledge.uky.edu/markey_facpub/509