β-Hydroxybutyrate Attenuates Cardiac Inflammation and Hepatic Fibrosis in Dahl Salt-Sensitive Rats.

Hypertension remains a major driver of multi-organ damage, including cardiac remodeling and hepatic complications. The ketone body β-hydroxybutyrate (BHB) has emerged as a potential metabolic signaling molecule with anti-inflammatory properties. This study investigated whether BHB attenuates cardiac stress and hepatic injury in a salt-sensitive hypertensive model. Dahl salt-sensitive (DS) rats were fed a high-salt (HS) diet combined with a choline-deficient diet to induce cardiac inflammation and hepatic fibrosis. Rats received either BHB or a control vehicle. We found that BHB significantly suppressed hepatic lipid accumulation and fibrotic markers, including TGF-β and collagen III mRNA, even under severe dietary stress. In the heart, BHB attenuated the expression of inflammatory markers (TNF-α and ANP) despite the persistence of high systolic blood pressure. These results demonstrate that BHB exerts direct organ-protective effects through anti-inflammatory and anti-fibrotic actions that are independent of robust blood pressure reduction. Our findings suggest that BHB could be a promising metabolic intervention for managing multi-organ complications in hypertensive patients with metabolic comorbidities.