info:eu-repo/semantics/article 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-3b, was re-activated by both LC diets; however, the Fat-LC, but not the Pro-LC, diet exerted cardioprotec-tion in GSK-3b cardiac-specific knockout mice. b-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. Free full text at PMC https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8861266/ Appendix: https://unilib.phaidrabg.rs/o:3424 https://unilib.phaidrabg.rs/o:2919 doi:10.1093/cvr/cvaa298 cobiss:125539081 ISSN: 0008-6363 Key words: low-carbohydrate diet, cardiac hypertrophy, heart failure, ketone body 2021 application/pdf 1588018 bytes eng Dietary carbohydrates restriction inhibits the development of cardiac hypertrophy and heart failure Cardiovascular research 117(11) Nakamura, Michinari Odanović, Natalija Nakada, Yasuki Dohi, Satomi Zhai, Peiyong Ivessa, Andreas Yang, Zhi Abdellatif, Maha Sadoshima, Junichi http://creativecommons.org/licenses/by-nc/4.0/legalcode Podatak o licenci prema https://v2.sherpa.ac.uk/id/publication/321