Whole grain intake associated molecule 5-aminovaleric acid betaine decreases β-oxidation of fatty acids in mouse cardiomyocytes.
Whole grain intake associated molecule 5-aminovaleric acid betaine decreases β-oxidation of fatty acids in mouse cardiomyocytes.
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DOI：
10.1038/s41598-018-31484-5
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发表时间：
2018-08-29
影响因子：
4.6
通讯作者：
Hanhineva K
中科院分区：
文献类型：
--
作者：
Kärkkäinen O;Tuomainen T;Koistinen V;Tuomainen M;Leppänen J;Laitinen T;Lehtonen M;Rysä J;Auriola S;Poso A;Tavi P;Hanhineva K
尽管流行病学证据表明，富含全谷物的饮食可以降低慢性生活方式相关疾病的风险，但这些积极影响的生物学机制大多尚不清楚。血浆和心脏等代谢活跃组织中5-氨基戊酸甜菜碱(5-AVAB)水平的增加与摄入富含全谷物的饮食有关。然而，5-AVAB的生物学效应却知之甚少。我们用质谱仪评估了人和小鼠心脏组织中5-AVAB的浓度(分别为3-22 微米和38-78 微米)。我们发现，在生理浓度范围内，5-AVAB呈剂量依赖性地抑制由脂肪酸β氧化引起的氧耗，但不影响线粒体呼吸，根据培养的小鼠原代心肌细胞的氧耗率来衡量。我们还证明，这种作用是由于5-AVAB诱导细胞内L肉碱的减少所致。在培养的心肌细胞中，L肉碱水平的降低至少部分是通过抑制细胞膜肉碱转运蛋白(OCTN_2)和siRNA介导的OCTN_2沉默来实现的。5-AVAB抑制脂肪酸的β氧化是富含全谷类食物调节体内能量代谢的新机制。要阐明5-AVAB对心脏生理学的潜在益处，还需要进一步的活体研究。
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.
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DOI：
10.1136/bmj.i2716
发表时间：
2016-06-14
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Aune D;Keum N;Giovannucci E;Fadnes LT;Boffetta P;Greenwood DC;Tonstad S;Vatten LJ;Riboli E;Norat T
通讯作者：
Norat T
DOI：
10.1016/0005-2736(77)90257-7
发表时间：
1977-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
MOLSTAD, P;BOHMER, T;EIKLID, K
通讯作者：
EIKLID, K
影响因子：
14.8
作者：
通讯作者：
--
影响因子：
2.2
作者：
HUBINGER, A;WEIKERT, G;GRIES, FA
通讯作者：
GRIES, FA
影响因子：
7.3
作者：
Tars, Kaspars;Leitans, Janis;Pugovics, Osvalds
通讯作者：
Pugovics, Osvalds