Journal article
Authors list: Gutgesell, A; Wen, GP; König, B; Koch, A; Spielmann, J; Stangl, GI; Eder, K; Ringseis, R
Publication year: 2009
Pages: 1206-1216
Journal: Biochimica et Biophysica Acta (BBA) - General Subjects
Volume number: 1790
Issue number: 10
ISSN: 0304-4165
DOI Link: https://doi.org/10.1016/j.bbagen.2009.06.012
Publisher: Elsevier
Abstract:
Background: Hepatic PPAR alpha acts as the primary mediator of the adaptive response to fasting by upregulation of a number of genes involved in fatty acid catabolism. Whether carnitine-acylcarnitine translocase (CACT), which mediates the import of acylcarnitines into the mitochondrial matrix for subsequent beta-oxidation of fatty acid moieties, is also regulated by PPAR alpha in the liver has not yet been investigated.Methods and Results: Herein, we observed that hepatic mRNA abundance of CACT was increased by both, fasting and treatment with PPAR alpha agonist VVY-14,643 in wild-type mice but not PPAR alpha-knockout mice (P<0.05). Cell culture experiments revealed that CACT mRNA abundance was higher in liver cells treated with either WY-14,643 or PPAR delta agonist GW0742, but not with PPAR-gamma agonist troglitazone (TGZ) than in control cells (P<0.05). In addition, reporter assays revealed activation of mouse CACT promoter by Wy14,643 and GW0742, but not TGZ. Moreover, deletion and mutation analyses of CACT promoter and 5'-UTR revealed one functional PPRE in the 5'-UTR of mouse CACT.General significance: CACT is upregulated by PPAR alpha and PPAR delta, probably by binding to a functional PPRE at position + 45 to + 57 relative to the transcription start site. The upregulation of CACT by PPAR alpha and PPAR delta, which are both important for the regulation of fatty acid oxidation in tissues during fasting, may increase the import of acylcarnitine into the mitochondrial matrix during fasting. (C) 2009 Elsevier B.V. All rights reserved.
Citation Styles
Harvard Citation style: Gutgesell, A., Wen, G., König, B., Koch, A., Spielmann, J., Stangl, G., et al. (2009) Mouse carnitine-acylcarnitine translocase (CACT) is transcriptionally regulated by PPARα and PPARδ in liver cells, Biochimica et Biophysica Acta (BBA) - General Subjects, 1790(10), pp. 1206-1216. https://doi.org/10.1016/j.bbagen.2009.06.012
APA Citation style: Gutgesell, A., Wen, G., König, B., Koch, A., Spielmann, J., Stangl, G., Eder, K., & Ringseis, R. (2009). Mouse carnitine-acylcarnitine translocase (CACT) is transcriptionally regulated by PPARα and PPARδ in liver cells. Biochimica et Biophysica Acta (BBA) - General Subjects. 1790(10), 1206-1216. https://doi.org/10.1016/j.bbagen.2009.06.012