Peroxisome deficiency causes a complex phenotype because of hepatic SREBP/Insig dysregulation associated with endoplasmic reticulum stress.

ABSTRACT: Regulation of hepatic cholesterol biosynthesis, lipogenesis, and insulin signaling intersect at the transcriptional level by control of SREBP and Insig genes. We previously demonstrated that peroxisome-deficient PEX2-/- mice activate SREBP-2 pathways but are unable to maintain normal cholesterol homeostasis. In this study, we demonstrate that oral bile acid treatment normalized hepatic and plasma cholesterol levels and hepatic cholesterol synthesis in early postnatal PEX2 mutants, but SREBP-2 and its target gene expressions remained increased. SREBP-2 pathway induction was also observed in neonatal and longer surviving PEX2 mutants, where hepatic cholesterol levels were normal. Abnormal expression patterns for SREBP-1c and Insig-2a, and novel regulation of Insig-2b, further demonstrate tha

SUBMITTER: Kovacs WJ 

PROVIDER: S-EPMC2652311 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature