Whole grain intake associated molecule 5-aminovaleric acid betaine decreases ß-oxidation of fatty acids in mouse cardiomyocytes
Files
Self archived version
published versionDate
2018Author(s)
Unique identifier
10.1038/s41598-018-31484-5Metadata
Show full item recordMore information
Self-archived item
Citation
Kärkkäinen, Olli. Tuomainen, Tomi. Koistinen, Ville. Tuomainen, Marjo. Leppänen, Jukka. Laitinen, Tuomo. Lehtonen, Marko. Rysä, Jaana. Auriola, Seppo. Poso, Antti. Tavi, Pasi. Hanhineva, Kati. (2018). Whole grain intake associated molecule 5-aminovaleric acid betaine decreases ß-oxidation of fatty acids in mouse cardiomyocytes. Scientific reports, 8, 13036. 10.1038/s41598-018-31484-5.Rights
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 mechanism on how diets rich in whole grains may regulate energy metabolism in the body. Elucidating potentially beneficial effects of 5-AVAB e.g. on cardiac physiology will require further in vivo investigations.
Link to the original item
http://dx.doi.org/10.1038/s41598-018-31484-5Publisher
Springer Nature America, IncCollections
- Terveystieteiden tiedekunta [1735]