Functional differences between l- and d-carnitine in metabolic regulation evaluated using a low-carnitine Nile tilapia model
Functional differences between l- and d-carnitine in metabolic regulation evaluated using a low-carnitine Nile tilapia model
复制标题
使用低肉碱尼罗罗非鱼模型评估左旋肉碱和右旋肉碱在代谢调节中的功能差异
DOI：
10.1017/s000711451900148x
复制
发表时间：
2019-09-28
影响因子：
3.6
通讯作者：
Du, Zhen-Yu
中科院分区：
文献类型：
--
作者：
Li, Jia-Min;Li, Ling-Yu;Du, Zhen-Yu
左旋肉碱是线粒体β-氧化所必需的，已被用作人类和养殖动物的降脂饲料添加剂。左旋肉碱是左旋肉碱的光学异构体，广泛应用于动物饲料中。然而，由于左旋肉碱的内源性背景，左旋肉碱和右旋肉碱之间的功能差异很难研究。在本研究中，我们开发了一个低肉毒碱尼罗罗非鱼模型，通过处理鱼与肉毒碱合成抑制剂，并使用该模型来研究功能之间的差异l-和d-肉毒碱在鱼的营养代谢。将L-或D-肉毒碱（0中心点4g/kg饮食）喂给低肉毒碱罗非鱼6周。结果表明，低肉碱罗非鱼肝脏中酰基肉碱含量从3522 ng/g增加到10822 ng/g，脂肪沉积量从15中心点89减少到11中心点97%。与L-肉毒碱组相比，D-肉毒碱组脂酰肉毒碱浓度从10 822 ng/g降低到5482 ng/g，脂质沉积量从11中心点97增加到20中心点21%，肝脏β-氧化和解毒相关基因的mRNA表达量增加。d-肉毒碱喂养还诱导肝脏炎症、氧化应激和细胞凋亡。代谢组学研究进一步表明，d-肉毒碱喂养增加糖酵解，蛋白质代谢和活性的三羧酸循环和氧化磷酸化。因此，l-肉毒碱可以在鱼中生理地利用，而d-肉毒碱作为异生物质代谢并诱导脂毒性。d-肉毒碱喂养的鱼表现出过氧化物酶体β-氧化，糖酵解和氨基酸降解的增加，以维持能量稳态。因此，d-肉碱不推荐用于养殖动物。
l-Carnitine is essential for mitochondrial beta-oxidation and has been used as a lipid-lowering feed additive in humans and farmed animals. d-Carnitine is an optical isomer of l-carnitine and dl-carnitine has been widely used in animal feeds. However, the functional differences between l- and d-carnitine are difficult to study because of the endogenous l-carnitine background. In the present study, we developed a low-carnitine Nile tilapia model by treating fish with a carnitine synthesis inhibitor, and used this model to investigate the functional differences between l- and d-carnitine in nutrient metabolism in fish. l- or d-carnitine (0 center dot 4 g/kg diet) was fed to the low-carnitine tilapia for 6 weeks. l-Carnitine feeding increased the acyl-carnitine concentration from 3522 to 10 822 ng/g and alleviated the lipid deposition from 15 center dot 89 to 11 center dot 97 % in the liver of low-carnitine tilapia. However, as compared with l-carnitine group, d-carnitine feeding reduced the acyl-carnitine concentration from 10 822 to 5482 ng/g, and increased lipid deposition from 11 center dot 97 to 20 center dot 21 % and the mRNA expression of the genes involved in beta-oxidation and detoxification in the liver. d-Carnitine feeding also induced hepatic inflammation, oxidative stress and apoptosis. A metabolomic investigation further showed that d-carnitine feeding increased glycolysis, protein metabolism and activity of the tricarboxylic acid cycle and oxidative phosphorylation. Thus, l-carnitine can be physiologically utilised in fish, whereas d-carnitine is metabolised as a xenobiotic and induces lipotoxicity. d-Carnitine-fed fish demonstrates increases in peroxisomal beta-oxidation, glycolysis and amino acid degradation to maintain energy homeostasis. Therefore, d-carnitine is not recommended for use in farmed animals.