Transcriptional regulation of peroxisome proliferator-activated receptors and liver X receptors

Abstract

Peroxisome proliferator-activated receptors (PPAR) and liver X receptors (LXR) regulate a plethora of biologic processes and key metabolic and physiologic events. Deregulation of their transcription and activity is commonly associated with dyslipidemic disorders, diabetes, cancer, and cardiovascular disease. This review addresses recent advances in our understanding of the molecular mechanisms regulating transcription of these nuclear receptors. The heterogeneity of factors regulating their transcription and activity suggests intricate regulatory networks that determine their tissue expression pattern and their responses to pharmacologic agents. Understanding such mechanisms will facilitate unraveling their protective effects in disease as well as the design of effective targeted therapies.

Peroxisome proliferator-activated receptor γ1 and γ2 isoforms alter lipogenic gene networks in goat mammary epithelial cells to different extents

“…In rats (Repa et al, 2000;Fiévet and Staels, 2009) and bovine mammary cells (McFadden and Corl, 2010), NR1H3 enhances the expression of SREBF1. Other studies reported cross-talk between NR1H3 and PPARG (Villacorta et al, 2007), and NR1H3 can be regulated by PPARG (Chawla et al, 2001). The effect of PPARG on SREBF1 in turn could be mediated by NR1H3 (Kast-Woelbern et al, 2004).…”

UPR Pathways Combine to Prevent Hepatic Steatosis Caused by ER Stress-Mediated Suppression of Transcriptional Master Regulators

“…Indeed, potential binding sites for C/ebp α exist in the promoters of Ppar α and Srebp1 (Villacorta et al, 2007). It seems most plausible that ER stress will lead to suppression of C/ebp α partially through CHOP, and consequent suppression of other master regulators of metabolic gene expression such as Srebp1 , Ppar α, and Pgc1 α.…”

Induction of Liver Steatosis and Lipid Droplet Formation in ATF6α-Knockout Mice Burdened with Pharmacological Endoplasmic Reticulum Stress

“…CHOP expression suppresses C/EBPα because CHOP can function as a dominant-negative regulator of C/EBP family members (Ron and Habener, 1992). This in turn leads to the suppression of metabolic gene expression through the suppressed expression of their master regulators, such as SREBP-1 and PPARα, via possible transcriptional control: it was shown previously that C/EBPα binding sites seem to exist on their promoter regions (Villacorta et al , 2007). Because PPARα is a master transcriptional regulator of genes involved in β-oxidization in mitochondria and peroxisomes (Reddy and Rao, 2006; Duval et al , 2007), suppression of its expression contributes to the accumulation of fatty acids.…”