NR1H2 & NR1H3 regulate gene expression linked to gluconeogenesis

Activation of liver X receptor α (LXRα, NR1H3) alters the expression of genes in liver and adipose tissue that collectively may limit hepatic glucose output and improve peripheral glucose uptake (Laffitte BA et al. 2003). In the liver, activation of NR1H3 led to the suppression of the expression of genes involved in gluconeogenesis including glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PCK1 or PEPCK) (Laffitte BA et al. 2003; Dalen KT et al. 2003; Herzog B et al. 2007; Commerford et al. 2007). In adipose tissue, activation of NR1H3 led to the transcriptional induction of the insulin-sensitive glucose transporter, GLUT4 (Laffitte BA et al. 2003; Dalen KT et al. 2003). In contrast, basal expression of LXRβ (NR1H2) has been shown to be essential for the regulation of PCK1 by another nuclear receptor, the glucocorticoid receptor GR (NR3C1) (Patel et al. 2011; Patel et. al. 2017). The LXRs appear to have somewhat opposing roles in the regulation of PCK1 in the liver since NR1H3 (LXRα) activation represses PCK1 mRNA expression induced by glucocorticoids and NR1H2 (LXRβ) antagonism reduces glucocorticoid-induced PCK1 mRNA expression.

Summary from Reactome (R-HSA-9632974), read 2026-09-23.