Regulation of retinoid X receptor gamma expression by fed state in mouse liver

Biochem Biophys Res Commun. 2015 Feb 27;458(1):134-9. doi: 10.1016/j.bbrc.2015.01.082. Epub 2015 Jan 28.

Abstract

Glucose metabolism is balanced by glycolysis and gluconeogenesis with precise control in the liver. The expression of genes related to glucose metabolism is regulated primarily by glucose and insulin at transcriptional level. Nuclear receptors play important roles in regulating the gene expression of glucose metabolism at transcriptional level. Some of these nuclear receptors form heterodimers with RXRs to bind to their specific regulatory elements on the target promoters. To date, three isotypes of RXRs have been identified; RXRα, RXRβ and RXRγ. However, their involvement in the interactions with other nuclear receptors in the liver remains unclear. In this study, we found RXRγ is rapidly induced after feeding in the mouse liver, indicating a potential role of RXRγ in controlling glucose or lipid metabolism in the fasting-feeding cycle. In addition, RXRγ expression was upregulated by glucose in primary hepatocytes. This implies that glucose metabolism governed by RXRγ in conjunction with other nuclear receptors. The luciferase reporter assay showed that RXRγ as well as RXRα increased SREBP-1c promoter activity in hepatocytes. These results suggest that RXRγ may play an important role in tight control of glucose metabolism in the fasting-feeding cycle.

Keywords: Feeding; Glucose; Lipid metabolism; Liver; RXRγ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Eating / physiology*
  • Fasting / metabolism
  • Glucose / metabolism*
  • Glucose / pharmacology
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Liver / metabolism*
  • Liver X Receptors
  • Male
  • Mice, Inbred C57BL
  • Orphan Nuclear Receptors / metabolism
  • Promoter Regions, Genetic
  • Response Elements
  • Retinoid X Receptor gamma / genetics
  • Retinoid X Receptor gamma / metabolism*
  • Sterol Regulatory Element Binding Protein 1 / genetics
  • Sterol Regulatory Element Binding Protein 1 / metabolism

Substances

  • Liver X Receptors
  • Orphan Nuclear Receptors
  • Retinoid X Receptor gamma
  • Srebf1 protein, mouse
  • Sterol Regulatory Element Binding Protein 1
  • Glucose