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

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.