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β-Hydroxybutyrate Attenuates Cardiac Inflammation and Hepatic Fibrosis in Dahl Salt-Sensitive Rats
Satoyasu Ito1, Eri Manabe2, Toshiyuki Shikata3
1Division of Clinical Pharmacy, Department of Pharmacy, School of Pharmacy, Hyogo Medical University, Kobe 650-8530, Japan.
Insights
Beta-hydroxybutyrate (BHB) reduces organ damage in hypertension by acting as an anti-inflammatory and anti-fibrotic agent. This ketone body offers organ protection independent of blood pressure reduction, suggesting potential therapeutic benefits for hypertensive patients.
Area of Science:
- Cardiovascular Research
- Metabolic Health
- Organ Protection
Background:
- Hypertension is a significant cause of multi-organ damage, affecting the heart and liver.
- Ketone bodies, like beta-hydroxybutyrate (BHB), are recognized for their anti-inflammatory signaling properties.
- Metabolic dysfunction often accompanies hypertension, exacerbating organ complications.
Purpose of the Study:
- To investigate the protective effects of BHB against cardiac and hepatic injury in a salt-sensitive hypertension model.
- To determine if BHB can mitigate inflammation and fibrosis induced by a high-salt and choline-deficient diet.
- To assess BHB's impact on organ damage independent of its effect on blood pressure.
Main Methods:
- Dahl salt-sensitive (DS) rats were subjected to a high-salt (HS) diet and a choline-deficient diet.
- Rats were treated with either BHB or a control vehicle.
- Cardiac and hepatic tissues were analyzed for inflammatory markers, fibrotic markers, and lipid accumulation.
Main Results:
- BHB significantly reduced hepatic lipid accumulation and suppressed fibrotic markers (TGF-β, collagen III mRNA).
- BHB attenuated cardiac inflammatory markers (TNF-α, ANP) despite sustained high blood pressure.
- Organ-protective effects of BHB were observed even under severe dietary stress.
Conclusions:
- BHB demonstrates direct organ-protective effects in hypertension, mediated by anti-inflammatory and anti-fibrotic actions.
- These benefits are independent of significant blood pressure reduction.
- BHB represents a potential metabolic intervention for managing multi-organ complications in hypertensive patients with metabolic comorbidities.
Abstract:
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.
