Functional differences between l- and d-carnitine in metabolic regulation evaluated using a low-carnitine Nile tilapia model

l -carnitine is essential for mitochondrial β -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 (0·4 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 with l -carnitine group, d -carnitine feeding reduced the acyl-carnitine concentration from 10 822 to 5482 ng/g, and increased lipid deposition from 11·97 to 20·21 % and the mRNA expression of the genes involved in β -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 β -oxidation, glycolysis and amino acid degradation to maintain energy homeostasis. Therefore, d -carnitine is not recommended for use in farmed animals.