Whole grain intake associated molecule 5-aminovaleric acid betaine decreases β-oxidation of fatty acids in mouse cardiomyocytes

Scientific Reports
Olli KärkkäinenKati Hanhineva

Abstract

Despite epidemiological evidence showing that diets rich in whole grains reduce the risk of chronic life-style related diseases, biological mechanisms for these positive effects are mostly unknown. Increased 5-aminovaleric acid betaine (5-AVAB) levels in plasma and metabolically active tissues such as heart have been associated with consumption of diets rich in whole grains. However, biological effects of 5-AVAB are poorly understood. We evaluated 5-AVAB concentrations in human and mouse heart tissue (3-22 µM and 38-78 µM, respectively) using mass spectrometry. We show that 5-AVAB, at physiological concentration range, dose-dependently inhibits oxygen consumption due to β-oxidation of fatty acids, but does not otherwise compromise mitochondrial respiration, as measured with oxygen consumption rate in cultured mouse primary cardiomyocytes. We also demonstrate that this effect is caused by 5-AVAB induced reduction of cellular L-carnitine. Reduced L-carnitine levels are at least partly mediated by the inhibition of cell membrane carnitine transporter (OCTN2) as evaluated by in silico docking, and by siRNA mediated silencing of OCTN2 in cultured cardiomyocytes. 5-AVAB caused inhibition of β-oxidation of fatty acids is a novel mecha...Continue Reading

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Sep 27, 2018·The American Journal of Clinical Nutrition·Olli KärkkäinenKati Hanhineva

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Citations

Sep 25, 2020·Nature·Helen E VuongElaine Y Hsiao
Jun 4, 2020·Scientific Reports·Nunzia D'OnofrioGiuseppe Campanile
Oct 15, 2020·International Journal of Molecular Sciences·Francesca Di CristoGianfranco Peluso
Jan 22, 2019·Journal of Agricultural and Food Chemistry·Nunzia D'OnofrioGiuseppe Campanile

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Methods Mentioned

BETA
Transfection

Software Mentioned

MODELER
PSI
Maestro
Profinder
BLAST
Discovery Studio
Studio
MassHunter Workstation Acquisition
MassHunter
TASSER

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