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- Title
Dietary carbohydrates restriction inhibits the development of cardiac hypertrophy and heart failure.
- Authors
Nakamura, Michinari; Odanovic, Natalija; Nakada, Yasuki; Dohi, Satomi; Zhai, Peiyong; Ivessa, Andreas; Yang, Zhi; Abdellatif, Maha; Sadoshima, Junichi
- Abstract
Aims A diet with modified components, such as a ketogenic low-carbohydrate (LC) diet, potentially extends longevity and healthspan. However, how an LC diet impacts on cardiac pathology during haemodynamic stress remains elusive. This study evaluated the effects of an LC diet high in either fat (Fat-LC) or protein (Pro-LC) in a mouse model of chronic hypertensive cardiac remodelling. Methods and results Wild-type mice were subjected to transverse aortic constriction, followed by feeding with the Fat-LC, the Pro-LC, or a high-carbohydrate control diet. After 4 weeks, echocardiographic, haemodynamic, histological, and biochemical analyses were performed. LC diet consumption after pressure overload inhibited the development of pathological hypertrophy and systolic dysfunction compared to the control diet. An anti-hypertrophic serine/threonine kinase, GSK-3β, was re-activated by both LC diets; however, the Fat-LC, but not the Pro-LC, diet exerted cardioprotection in GSK-3β cardiac-specific knockout mice. β-hydroxybutyrate, a major ketone body in mammals, was increased in the hearts of mice fed the Fat-LC, but not the Pro-LC, diet. In cardiomyocytes, ketone body supplementation inhibited phenylephrine-induced hypertrophy, in part by suppressing mTOR signalling. Conclusion Strict carbohydrate restriction suppresses pathological cardiac growth and heart failure after pressure overload through distinct anti-hypertrophic mechanisms elicited by supplemented macronutrients.
- Subjects
HEART failure; CARDIAC hypertrophy; HIGH-carbohydrate diet; HIGH-fat diet; BUTYRATES; LABORATORY mice; THREONINE
- Publication
Cardiovascular Research, 2021, Vol 117, Issue 11, p2365
- ISSN
0008-6363
- Publication type
Article
- DOI
10.1093/cvr/cvaa298