o:2919 Dietary carbohydrates restriction inhibits the development of cardiac hypertrophy and heart failure en 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 Key words: low-carbohydrate diet, cardiac hypertrophy, heart failure, ketone body 91552100 125539081 1552101 0008-6363 1552099 10.1093/cvr/cvaa298 2023-10-06T18:38:39.453Z 44 yes 46 Michinari Nakamura 104967689 0000-0003-2005-3161 2021 46 Natalija Odanović 104968713 0000-0003-0343-6195 2021 46 Yasuki Nakada 0000-0003-0510-6923 46 Satomi Dohi 46 Peiyong Zhai 0000-0002-6482-2033 46 Andreas Ivessa 0000-0002-7578-1337 46 Zhi Yang 0000-0001-8905-3392 46 Maha Abdellatif 46 Junichi Sadoshima 0000-0003-3724-4132 application/pdf 1588018 https://unilib.phaidrabg.rs/o:2919 no yes 17 Podatak o licenci prema https://v2.sherpa.ac.uk/id/publication/321 70 612.396:616.12 92000001 71A11 Cardiovascular research 117 11 2365 2376 2021