Whole grain intake associated molecule 5-aminovaleric acid betaine decreases β-oxidation of fatty acids in mouse cardiomyocytes
Kärkkäinen O, Tuomainen T, Koistinen V, Tuomainen M, Leppänen J, Laitinen T, Lehtonen M, Rysä J, Auriola S, Poso A, Tavi P, Hanhineva K
Scientific reports · 40 citations
Review labels
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How it was studied
- Design
- In vitro/mechanistic study (classified by our AI screen)
- Studied in
- People, plus animal or lab work
- Main outcome
- Mechanisms only
Who paid for it
- Funding
- Independent funding
- University or hospital
- Biokeskus Kuopio, Itä-Suomen yliopisto
- Nonprofit
- Foundation for Cardiovascular Research
- University or hospital
- Itä-Suomen Yliopisto
- Nonprofit
- Alkoholitutkimussäätiö
- University or hospital
- Semmelweis Egyetem
- Government
- Academy of Finland
- Government
- Tekes
- Government
- China Scholarship Council
- Nonprofit
- Sydäntutkimussäätiö
- University or hospital
- Biocenter Finland
- Government
- Academy of Finland Tekes
- University or hospital
- Biocenter Kuopio
- University or hospital
- University of Eastern Finland
- Nonprofit
- The Finnish Foundation for Cardiovascular Research
Based on 14 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2018-08-23 · Sci Rep · vol. 8 · issue 1 · p. 13036
- Publisher
- Nature Portfolio
- Cited
- 50 citations · more than 85% of similar papers · 2.0× the field average
- References
- 24 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Metabolism and Genetic Disorders · Diet and metabolism studies · Metabolomics and Mass Spectrometry Studies
- Keywords
- Carnitine, Beta oxidation, In vivo, Metabolism, Betaine, Respiration, Chemistry, Biochemistry, Biology
- MeSH
- myocardium, cells, cultured, myocytes, cardiac, animals, mice, inbred c57bl, humans, betaine, fatty acids, amino acids, neutral, diet, oxidation-reduction, mass spectrometry, whole grains
12 authors
From FI, DE
- Olli K. Kärkkäinen · correspondingUniversity of Eastern Finland
- Tomi TuomainenUniversity of Eastern Finland
- Ville KoistinenUniversity of Eastern Finland
- Marjo H. TuomainenUniversity of Eastern Finland
- Jukka M. LeppänenUniversity of Eastern Finland
- Tuomo LaitinenUniversity of Eastern Finland
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.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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