Effects Of Two Parasitic Infection On Ketone Body Metabolism In Mice

Ketone body are intermediates of incomplete oxidation decomposition of fatty acids,including three components,acetoacetic acid,beta hydroxybutyric acid and acetone,It is mainly produced by mitochondria in liver parenchymal cells and transported to extrahepatic tissues such as brain,heart and skeletal muscle.Besides being used as raw materials for energy supply,ketone body also play a positive role as signal transduction mediators,as well as modulating inflammation and oxidative stress.Many studies have confirmed the important role of ketone body in mammalian cell metabolism,homeostasis and various physiological and pathological conditions.It is known that a variety of parasitic infections may cause abnormal ketoacid metabolism in the host,even ketoacid poisoning,causing serious harm to patients,but there is no clear research results on its pathogenesis.Therefore,in this study,a model of acute and chronic infection(including early and near death)infection in mice was established by selecting Trypanosoma evansi and Toxoplasma gondii in vitro.The ketone body in peripheral blood of mice were detected by electrochemical sensor;and the ketone body level was determined by spectrophotometry.After verifying the quality of the template and the specificity of primers,real-time fluorescence quantitative PCR was used to detect the transcriptional level of the 4 related enzyme genes(Acaa2,Hmgcl,Hmgcs2,and Bdh1)and the 3 related enzyme genes(Acaa2,Bdh1 and Oxct1)of the murine ketone body generation pathway.It was found that the mice infected with Trypanosoma 4V1 M could significantly inhibit the transcription of the gene Acaa2,Hmgcl,Hmgcs2 and Bdh1(p < 0.01),and significantly promote the transcriptional level of the key enzyme gene of the ketone body decomposition pathway,the gene Oxct1(p < 0.05),reduce the ketone body format Oxct1 the Bdh1 liver and promote the decomposition of ketone body in the brain tissue.Therefore,Trypanosomiasis can cause ketone levels in the peripheral blood of the host,which will not cause ketoacidosis in the host.The chronic infection of Toxoplasma gondii strain RH can significantly increase the transcriptional level of Acaa2,Hmgcl,Hmgcs2 and Bdh1(p < 0.01),which can reduce the transcriptional level of Acaa2,Oxct1 and Bdh1(p < 0.01),to promote the formation of the ketone body in the host liver and reduce the decomposition in the host brain tissue.The content of ketone body in the blood of the host increased significantly.Therefore,Toxoplasma gondii infection can cause ketoacidosis in the host.This study is the first time to analyze the effect of parasitic protozoa infection on the transcriptional level of ketone body and decomposition pathway related enzymes in mice from the host's point of view,and to explore the mechanism of the abnormality of ketone body,provide reference for screening of diagnostic markers for host ketone metabolism in parasite infection.