Dietary carbohydrates restriction inhibits the development of cardiac hypertrophy and heart failure

Michinari Nakamura, Natalija Odanovic, Yasuki Nakada, Satomi Dohi, Peiyong Zhai, Andreas Ivessa, Zhi Yang, Maha Abdellatif, Junichi Sadoshima

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2365-2376
Number of pages12
JournalCardiovascular research
Issue number11
StatePublished - Oct 1 2021

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


  • Cardiac hypertrophy
  • Heart failure
  • Ketone body
  • Low-carbohydrate diet


Dive into the research topics of 'Dietary carbohydrates restriction inhibits the development of cardiac hypertrophy and heart failure'. Together they form a unique fingerprint.

Cite this