Title: Coordinate induction of PPAR alpha and SREBP2 in multifunctional protein 2 deficient mice
Authors: Martens, Katrin ×
Ver Loren van Themaat, Emiel
van Batenburg, Marinus F
Heinäniemi, Merja
Huyghe, Steven
Van Hummelen, Paul
Carlberg, Carsten
Van Veldhoven, Paul P
Van Kampen, Antoine
Baes, Myriam #
Issue Date: 2008
Publisher: Elsevier Science
Series Title: Biochimica et Biophysica Acta. Molecular and Cell Biology of Lipids vol:1781 issue:11-12 pages:694-702
Abstract: Mice with inactivation of the D-specific multifunctional protein 2 (MFP2), a crucial enzyme of peroxisomal beta-oxidation, develop multiple pathologies in diverse tissues already starting in the postnatal period. Gene expression profiling performed on liver of 2-day-old pups revealed up-regulation of PPAR alpha responsive genes in knockout mice. Surprisingly, also genes involved in cholesterol biosynthesis were markedly induced. Real-time PCR confirmed the induction of PPAR alpha target genes and of HMGCR and SREBP2, both involved in cholesterol synthesis, in lactating and in adult MFP2 knockout mice. In accordance, the rate of cholesterol biosynthesis was significantly increased in liver of knockout mice but the hepatic cholesterol concentration was unaltered. In MFP2/PPAR alpha double knockout mice, up-regulations of SREBP2 and HMGCR were markedly attenuated. These data demonstrate a tight interrelationship between induction of PPAR alpha by endogenous ligands and up-regulation of genes of cholesterol biosynthesis through increased expression of SREBP2.
ISSN: 1388-1981
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Lipid Biochemistry and Protein Interactions
Cell Metabolism
Centre for Educational Development (-)
× corresponding author
# (joint) last author

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