Effect of Ketone Bodies on Mitochondrial Cardiomyopathy and Heart Aging
Abstract
In this study, we used a novel mouse model of mitochondrial cardiomyopathy (transgenic mice overexpressing TMEM135; Tg-TMEM135) to test whether the heart disease can be prevented by supplementation of ketone body, which is a metabolite of one of the branched chain amino acids (BCAAs) whose metabolism is decreased in the heart of these mice. We also tested whether ketone body supplementation prevents pathologies associated with aging of the heart. Our results indicate that ketone body supplementation improved left ventricle hypertrophy of the heart, vacuole formation in the heart muscle, and the survival of Tg-TMEM135 mice. In aged mice, the left ventricle volume and mass showed increase compared to young mice. These measurements were significantly reduced in aged mice with ketone body supplementation, suggesting that ketone body supplementation may improve aging-associated hypertrophy of the heart. These findings suggest the possibility that ketone body supplementation may be effective in improving mitochondrial cardiomyopathy and heart abnormalities associated with aging in humans. Based on our finding that ketone body supplementation can substitute for impaired BCAA catabolism in Tg-TMEM135 mice, ketone body supplementation may be also effective in preventing cardiovascular disease in patients with impaired BCAA metabolism, which is being suggested as a risk factor/biomarker for cardiovascular disease.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2019
- Accession Number
- AD1094717
Entities
People
- Akihiro Ikeda
Organizations
- University of Wisconsin System