Carnitine Palmitoyltransferase 1 facilitates fatty acid oxidation in a noncell autonomous manner [TKO_RNAseq]

Mitochondrial fatty acid oxidation is facilitated by the combined activities of Carnitine Palmitoyltransferase 1 and Carnitine Palmitoyltransferase 2 which generate and utilize acylcarnitines respectively. We compared the response of mice with liver specific deficiencies in Cpt1a and Cpt1b, Cpt2, or the triple deletion of all three acyltransferases. We discovered that they display unique metabolic, physiological and molecular phenotypes. The loss of Cpt1a and Cpt1b or Cpt2 resulted in particular transcriptional outputs in hepatocytes. We show that much of the transcriptional signature is suppressed when deleting both Cpt2 and Ppara, showing the contribution of Ppara. Our results utilize stringent genetic mouse models to characterize the differential phenotypes of mice lacking Cpt1a and Cpt1b or Cpt2 and also show the contribution of a major transcription factor, Ppara. To characterize transcriptional contribution of Cpt1 or Cpt2, littermate control mice and mice lacking Cpt1a and Cpt1b, Cpt2, all three Cpt1a Cpt1b and Cpt2, or Cpt2 and Ppara were fasted for 24 hours and livers were collected for RNA-sequencing by Novogene Corporation Inc.