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- _4 label "Selventa" provenance.
- large_corpus.bel rights "Copyright (c) 2011-2012, Selventa. All rights reserved." provenance.
- _3 value "The KK/San obese and diabetic mouse, a mutant strain from KK obese mice, exhibits significantly low plasma triglyceride levels. In KK/San mice, genetic analysis identified a mutation in the gene encoding angiopoietin-like protein 3 (Angptl3), a liver-specific secretory protein. Treatment with Angptl3 protein increased plasma triglyceride in wild-type and KK/San mice. Angptl3 inactivated lipoprotein lipase (LPL), resulting in decreased hydrolysis and rise of plasma triglyceride. In the current study, natural and synthetic ligands for LXR augmented Angptl3 mRNA expression and protein production in hepatoma cells. LXR ligands and LXR/RXR complex increased the promoter activity of Angptl3 gene. Motif search and serial deletion of Angptl3 promoter identified an LXR response element (LXRE). Point mutation in the LXRE abolished the ligand-mediated transactivation of Angptl3 promoter. Gel mobility shift assay showed the direct binding of LXR/RXR complex to the LXRE of the Angptl3 promoter. Furthermore, treatment of mice with synthetic LXR ligand caused triglyceride accumulation in the liver and plasma, which was accompanied by induction of hepatic mRNAs of several LXR-target genes, including sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase (FAS), and Angptl3. In Angptl3 deficient C57BL/6J mice, LXR ligand did not cause hypertriglyceridemia but accumulation of triglyceride in the liver. Our results demonstrate that Angptl3 is a direct target of LXR, and that induction of hepatic Angptl3 accounts for hypertriglyceridemia associated with the treatment of LXR ligand." provenance.
- _3 wasQuotedFrom 12672813 provenance.
- assertion hadPrimarySource 12672813 provenance.
- large_corpus.bel title "BEL Framework Large Corpus Document" provenance.
- large_corpus.bel description "Approximately 61,000 statements." provenance.
- assertion wasDerivedFrom large_corpus.bel provenance.
- assertion wasDerivedFrom _3 provenance.
- large_corpus.bel authoredBy _4 provenance.
- large_corpus.bel version "20131211" provenance.