Functional differences betweenl- andd-carnitine in metabolic regulation evaluated using a low-carnitine Nile tilapia model

Abstract

Abstractl-Carnitine is essential for mitochondrialβ-oxidation and has been used as a lipid-lowering feed additive in humans and farmed animals.d-Carnitine is an optical isomer ofl-carnitine anddl-carnitine has been widely used in animal feeds. However, the functional differences betweenl- andd-carnitine are difficult to study because of the endogenousl-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 betweenl- andd-carnitine in nutrient metabolism in fish.l- ord-carnitine (0·4 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 15·89 to 11·97 % in the liver of low-carnitine tilapia. However, as compared withl-carnitine group,d-carnitine feeding reduced the acyl-carnitine concentration from 10 822 to 5482 ng/g, and increased lipid deposition from 11·97 to 20·21 % and the mRNA expression of the genes involved inβ-oxidation and detoxification in the liver.d-Carnitine feeding also induced hepatic inflammation, oxidative stress and apoptosis. A metabolomic investigation further showed thatd-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, whereasd-carnitine is metabolised as a xenobiotic and induces lipotoxicity.d-Carnitine-fed fish demonstrates increases in peroxisomalβ-oxidation, glycolysis and amino acid degradation to maintain energy homeostasis. Therefore,d-carnitine is not recommended for use in farmed animals.