Background Impaired hepatic fatty acid metabolism and persistent mitochondrial dysfunction are phenomena commonly associated with liver failure. Decreased serum levels of L-carnitine, a amino acid derivative involved in fatty-acid and energy metabolism, have been reported in severe burn patients. The current study aimed to evaluate the effects of L-carnitine supplementation on mitochondrial damage and other hepatocyte injuries following severe burns and the related mechanisms. Methods Serum carnitine and other indicators of hepatocytic injury, including AST, ALT, LDH, TG, and OCT, were analyzed in severe burn patients and healthy controls. A burn model was established on the back skin of rats; thereafter, carnitine was administered, and serum levels of the above indicators were evaluated along with Oil Red O and TUNEL staining, transmission electron microscopy, and assessment of mitochondrial membrane potential and carnitine palmitoyltransferase 1 (CPT1) activity and expression levels in the liver. HepG2 cells pretreated with the CPT1 inhibitor etomoxir were treated with or without carnitine for 24 h. Next, the above indicators were examined, and apoptotic cells were analyzed via flow cytometry. High-throughput sequencing of rat liver tissues identified several differentially expressed genes (Fabp4, Acacb, Acsm5, and Pnpla3) were confirmed using RT-qPCR. Results Substantially decreased serum levels of carnitine and increased levels of AST, ALT, LDH, and OCT were detected in severe burn patients and the burn model rats. Accumulation of TG, evident mitochondrial shrinkage, altered mitochondrial membrane potential, decreased ketogenesis, and reduced CPT1 activity were detected in the liver tissue of the burned rats. Carnitine administration recovered CPT1 activity and improved all indicators related to cellular and fatty acid metabolism and mitochondrial injury. Inhibition of CPT1 activity with etomoxir induced hepatocyte injuries similar to those in burn patients and burned rats; carnitine supplementation restored CPT1 activity and ameliorated these injuries. The expression levels of the differentially expressed genes Fabp4, Acacb, Acsm5, and Pnpla3 in the liver tissue from burned rats and etomoxir-treated hepatocytes were also restored by treatment with exogenous carnitine. Conclusion Exogenous carnitine exerts protective effects against severe burn-induced cellular, fatty-acid metabolism, and mitochondrial dysfunction of hepatocytes by restoring CPT1 activity.

Background : Impaired liver fatty acid metabolism and persistent mitochondrial dysfunction are common phenomena and associated with liver failure. Decreased serum L-carnitine, a vitamin involved in fatty-acid and energy metabolisms, has been reported in severe burn patients. The current research aimed to study the effects and mechanism of L-carnitine on mitochondrial damage and other hepatocytic injuries. Methods : Serum carnitine and indicators for hepatocytic injuries including AST, ALT, LDH, TG and OCT in severe burn patients and healthy controls were analyzed. The burn model in rats was established by skin scalding, and the carnitine was administered to the rats. The indicators mentioned above in the serum, and oil red staining, TUNEL staining and TEM observation, mitochondrial membrane potential, and CPT1 activity as well as CPT1 expression of the liver tissue were examined. HepG2 cells, treated with the CPT1 inhibitor etomoxir, were supplied with/without carnitine for 24h. The indicators mentioned above were examined, and apoptotic cells were analyzed by flow cytometry. Transcriptom high throughput sequencing of the rat liver tissues was performed, and differentially expressed genes Fabp4, Acacb, Acsm5 and Pnpla3 were further determined by RT-qPCR. Results : Significantly decreased carnitine and increased AST, ALT, LDH and OCT in the serum were detected in the severe burn patients and the scalded rats. Accumulation of TG, obvious mitochondrial shrinking, altered mitochondrial membrane potential, decreased ketogenesis and declined CPT1 activity were found in the liver tissue of the scalded rats. Administration of carnitine recovered CPT1 activity and improved all the parameters for cellular, fatty acid metabolic and mitochondrial injuries. Inhibition of CPT1 activity with etomoxir in vitro induced similar hepatocytic injuries found in the burn patients and the scalded rats, and supplementation of carnitine restored CPT1 activity and ameliorated these injuries. Differentially expressed genes Fabp4, Acacb, Acsm5 and Pnpla3 in the liver tissue and in the etomoxir-treated hepatocytes were also restored by exogenous carnitine. Conclusion : Exogenous carnitine exerts its protective effect on severe burn-induced cellular, fatty-acid metabolic and mitochondrial dysfunction of the hepatocytes via restore of CPT1 activity.