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

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.