TY - JOUR
T1 - Coordinate induction of PPAR alpha and SREBP2 in multifunctional protein 2 deficient mice
AU - Martens, Katrin
AU - Ver Loren van Themaat, Emiel
AU - van Batenburg, Marinus F.
AU - Heinäniemi, Merja
AU - Huyghe, Steven
AU - van Hummelen, Paul
AU - Carlberg, Carsten
AU - van Veldhoven, Paul P.
AU - van Kampen, Antoine
AU - Baes, Myriam
PY - 2008
Y1 - 2008
N2 - 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
AB - 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
U2 - https://doi.org/10.1016/j.bbalip.2008.07.010
DO - https://doi.org/10.1016/j.bbalip.2008.07.010
M3 - Article
C2 - 18773970
SN - 1388-1981
VL - 1781
SP - 694
EP - 702
JO - BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
JF - BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
IS - 11-12
ER -