Retinoid X receptor: the forgotten partner in regulating lipid metabolism?
Am J Clin Nutr. 2015 Jun 10; Authors: Neuschwander-Tetri BA
People with non-alcoholic fatty liver disease have lower circulating RA concentrations than do normal controls.
The differences were not trivial, with concentrations in those having severe NASH being less than half the concentrations in controls.
Hepatic expression of the retinoid X receptor (RXR) was decreased in patients with NASH at the mRNA and protein levels, suggesting impaired signaling by RXR at multiple levels.
Ample animal evidence had shown that RXR, which is activated by RA and other lipids, has wide-ranging effects on virtually all aspects of the regulation of lipid metabolism.
The nuclear receptors that regulate the genes responsible for fat metabolism throughout the body [i.e., peroxisome proliferator–activated receptor (PPAR) c, PPARa, PPARd, farnesoid X receptor (FXR), and liver X receptor (LXR)] are bound to their cognate DNA response elements mostly as heterodimers with RXR!
The interaction of the 2 nuclear receptors in the heterodimer pair is considered “permissive,” meaning that the presence of ligand for both is not necessary, but when ligands for both receptors are present the resulting gene expression is greatly amplified!
PMID: 26063689 [PubMed – as supplied by publisher]
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The usual American diet is low in Vitamin A – among other nutrients.
The retinoids are forms of Vitamin A in the body. It stimulates retinoid X receptor (RXR)s.
People with non-alcoholic fatty liver disease have lower circulating RA concentrations than do normal controls.
The differences were not trivial, with concentrations in those having severe NASH being less than half the concentrations in controls.
Hepatic expression of the retinoid X receptor (RXR) was decreased in patients with NASH at the mRNA and protein levels, suggesting impaired signaling by RXR at multiple levels.
Liu et al. (2) undertook their study of RA concentrations and RXR expression because ample animal evidence had shown that RXR, which is activated by RA and other lipids, has wide-ranging effects on virtually all aspects of the regulation of lipid metabolism (3).
The nuclear receptors that regulate the genes responsible for fat metabolism throughout the body [i.e., peroxisome proliferator–activated receptor (PPAR) c, PPARa, PPARd, farne- soid X receptor (FXR), and liver X receptor (LXR)] are bound to their cognate DNA response elements mostly as heterodimers with RXR!
The interaction of the 2 nuclear receptors in the heterodimer pair is considered “permissive,” meaning that the presence of ligand for both is not necessary, but when ligands for both receptors are present the resulting gene expression is greatly amplified!