Li, J.-M.Li, L.-Y.Zhang, Y.-XJiang, Z.-YSamwel Mchele LimbuQiao, FDegrace, P.Chen, L.-Q.Zhang, M.-L.Du Z.-Y.2021-04-172021-04-172019-08-14Li, J.-M., Li, L.-Y., Zhang, Y.-X., Jiang, Z.-Y., Limbu, S.M., Qiao, F., Degrace, P., Chen, L.-Q., Zhang, M.-L. and Du Z.-Y. (2019). Functional differences between l- and d-carnitine in metabolic regulation evaluated using a low-carnitine Nile tilapia model. British Journal of Nutrition, 122(6): 625-638. https://doi.org/10.1017/S000711451900148Xhttp://hdl.handle.net/20.500.11810/5604l-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.Low-carnitine tilapiaMetabolic regulationL-carnitineD-carnitineNutrient metabolismcarnitine palmitoyltransferase 1fatty acidsMildronate (3-(2,2,2-trimethylhydrazinium) propionate)Journal Article, Peer Reviewedhttps://doi.org/10.1017/S000711451900148X