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Full-Text Articles in Life Sciences
Enzymatic Reduction Of Oxysterols Impairs Lxr Signaling In Cultured Cells And The Livers Of Mice., Guoxun Chen
Enzymatic Reduction Of Oxysterols Impairs Lxr Signaling In Cultured Cells And The Livers Of Mice., Guoxun Chen
Nutrition Publications and Other Works
Liver X receptors (LXRs) are nuclear receptors that play crucial roles in lipid metabolism in vivo and are activated by oxysterol ligands in vitro. The identity of the ligand that activates LXRs in vivo is uncertain. Here we provide two lines of evidence that oxysterols are LXR ligands in vitro and in vivo. First, overexpression of an oxysterol catabolic enzyme, cholesterol sulfotransferase, inactivates LXR signaling in several cultured mammalian cell lines but does not alter receptor response to the nonsterol agonist T0901317. Adenovirus-mediated expression of the enzyme in mice prevents dietary induction of hepatic LXR target genes by cholesterol but …
Central Role For Liver X Receptor In Insulin-Mediated Activation Of Srebp-1c Transcription And Stimulation Of Fatty Acid Synthesis In Liver., Guoxun Chen
Nutrition Publications and Other Works
Transcription of the gene encoding sterol regulatory element-binding protein 1c (SREBP-1c) is known to be activated by insulin in the liver. The resultant SREBP-1c protein activates transcription of the genes required for fatty acid synthesis. Here, we use SREBP-1c promoter reporter constructs to dissect the mechanism of insulin activation in freshly isolated rat hepatocytes. The data show that a complete insulin response (increase of 6- to 11-fold) requires two binding sites for liver X receptors (LXRs), which are nuclear receptors that are activated by oxygenated sterols. Disruption of these binding sites did not lower basal transcription but severely reduced the …