Acetylation contributes to hypertrophy-caused maturational delay of cardiac energy metabolism

JCI Insight
Arata FukushimaG D Lopaschuk

Abstract

A dramatic increase in cardiac fatty acid oxidation occurs following birth. However, cardiac hypertrophy secondary to congenital heart diseases (CHDs) delays this process, thereby decreasing cardiac energetic capacity and function. Cardiac lysine acetylation is involved in modulating fatty acid oxidation. We thus investigated what effect cardiac hypertrophy has on protein acetylation during maturation. Eighty-four right ventricular biopsies were collected from CHD patients and stratified according to age and the absence (n = 44) or presence of hypertrophy (n = 40). A maturational increase in protein acetylation was evident in nonhypertrophied hearts but not in hypertrophied hearts. The fatty acid β-oxidation enzymes, long-chain acyl CoA dehydrogenase (LCAD) and β-hydroxyacyl CoA dehydrogenase (βHAD), were hyperacetylated and their activities positively correlated with their acetylation after birth in nonhypertrophied hearts but not hypertrophied hearts. In line with this, decreased cardiac fatty acid oxidation and reduced acetylation of LCAD and βHAD occurred in newborn rabbits subjected to cardiac hypertrophy due to an aortocaval shunt. Silencing the mRNA of general control of amino acid synthesis 5-like protein 1 reduced acet...Continue Reading

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Citations

Aug 21, 2018·The Journal of Clinical Investigation·Bo Zhou, Rong Tian
Jun 21, 2019·The Biochemical Journal·Qutuba G KarwiGary D Lopaschuk
Mar 6, 2021·Frontiers in Nutrition·Josep Bassaganya-RieraMauro Serafini
Apr 4, 2021·Nutrition, Metabolism, and Cardiovascular Diseases : NMCD·Anderson Apolonio Silva PedrozaClaudia J Lagranha
Aug 20, 2021·Frontiers in Cardiovascular Medicine·Ezra B Ketema, Gary D Lopaschuk

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Methods Mentioned

BETA
acetylation
biopsy
gene knockdown
transfection
fluorescence microscopy
biopsies

Software Mentioned

ImageJ

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