Exogenous L-carnitine a meliorated burn-induced cellular and mitochondrial injuries of hepatocytes via recovering 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.