Low-carbohydrate diets containing plant-derived fat but not animal-derived fat ameliorate heart failure

Area of Science:

• Cardiology
• Nutritional Science
• Molecular Biology

Background:

• Cardiovascular disease (CVD) presents a significant global health challenge.
• Low-carbohydrate diets (LCDs) show promise for CVD risk reduction, but their role in preventing heart failure (HF) is not fully understood.

Purpose of the Study:

• To investigate the effects of different fat sources in LCDs on heart failure progression using a murine model.
• To elucidate the molecular mechanisms underlying the cardioprotective or cardiotoxic effects of LCDs.

Main Methods:

• Utilized a murine model of pressure overload-induced heart failure.
• Administered LCDs with either plant-derived (LCD-P) or animal-derived (LCD-A) fats.
• Analyzed gene expression related to fatty acid oxidation and peroxisome proliferator-activated receptor α (PPARα) activation.
• Performed loss- and gain-of-function experiments for PPARα.
• Investigated the role of stearic acid in activating PPARα in cardiomyocytes.

Main Results:

• LCD-P ameliorated HF progression, reducing inflammation and improving cardiac function.
• LCD-A aggravated inflammation and cardiac dysfunction.
• LCD-P induced higher expression of fatty acid oxidation genes and activated PPARα in the heart.
• PPARα activation was critical for preventing HF progression.
• Stearic acid, abundant in LCD-P, activated PPARα in cardiomyocytes.

Conclusions:

• The source of fat in LCDs critically influences HF outcomes.
• The plant-derived fat-stearic acid-PPARα pathway demonstrates a protective effect against HF.
• This pathway represents a potential therapeutic target for managing heart failure.