Iron scavenging and suppression of collagen cross-linking underlie antifibrotic effects of carnosine in the heart...

Area of Science:

• Cardiovascular Science
• Metabolic Disease Research
• Nutritional Biochemistry

Background:

• Oral histidyl dipeptides, like l-carnosine, are linked to cardiometabolic health, but mechanisms are unclear.
• Previous work showed carnosine analogs reduced liver fibrosis in obese mice.
• The cardiac antifibrotic effects and mechanisms of oral carnosine remain unknown.

Purpose of the Study:

• To investigate if oral carnosine mitigates adverse cardiac remodeling in diet-induced obesity.
• To explore the mechanisms underlying carnosine's potential cardioprotective effects in a mouse model mimicking metabolic syndrome.
• To assess carnosine's impact on cardiac fibrosis and oxidative stress markers.

Main Methods:

• Wild-type and GPx4+/- mice were fed standard or high-fat, high-sucrose diets for 16 weeks.
• Carnosine was administered in drinking water to a subset of obese mice.
• Cardiac remodeling, gene expression, protein carbonyls, iron levels, and collagen cross-linking were analyzed.

Main Results:

• Carnosine moderately improved glycemic control but not insulin sensitivity.
• Carnosine upregulated cardiac glutathione peroxidase 4 (GPx4) expression.
• Carnosine significantly reduced myocardial protein carbonyls and iron, and exhibited robust antifibrotic effects by suppressing collagen cross-linking.

Conclusions:

• Oral carnosine demonstrates antifibrotic potential in the heart during obesity.
• Carnosine may protect the heart by upregulating GPx4 and reducing oxidative stress and collagen cross-linking.
• These findings highlight carnosine as a potential therapeutic agent for obesity-related cardiac complications.