Retinoid X Receptors Intersect the Molecular Clockwork in the Regulation of Liver Metabolism

Overview

Journal Front Endocrinol (Lausanne)

Specialty Endocrinology

Date 2017 Mar 1

PMID 28243223

Citations 3

Authors

Salvatore De Cosmo

Gianluigi Mazzoccoli

Affiliations

Soon will be listed here.

Abstract

Liver metabolic pathways are driven by the biological clock, and appropriate timing of 24-h patterns of metabolic gene expression as well as anabolic/catabolic processes with wake-related activity/feeding and sleep-related resting/fasting cycles preserves hepatic healthiness. The interplay among the liver metabolic pathways and the molecular clockwork is geared by the nuclear receptors, and ligand-dependent transcription factors that gauge the cellular nutritional status and redox balance, bind hormones and metabolites, and modulate the transcription of thousands target genes through their DNA-binding domain. Several nuclear receptors in the liver oscillate with circadian rhythmicity, and among these, the retinoid X receptors play a key role in metabolism regulation, intersecting with the cogs of the molecular clockwork.

Citing Articles

Metabolomics Pilot Study Identifies Desynchronization of 24-H Rhythms and Distinct Intra-patient Variability Patterns in Critical Illness: A Preliminary Report.

Lusczek E, Parsons L, Elder J, Harvey S, Skube M, Muratore S Front Neurol. 2020; 11:533915.

PMID: 33123071 PMC: 7566909. DOI: 10.3389/fneur.2020.533915.

Nuclear Receptor Metabolism of Bile Acids and Xenobiotics: A Coordinated Detoxification System with Impact on Health and Diseases.

Garcia M, Thirouard L, Sedes L, Monrose M, Holota H, Caira F Int J Mol Sci. 2018; 19(11).

PMID: 30453651 PMC: 6274770. DOI: 10.3390/ijms19113630.

The Biological Clock: A Pivotal Hub in Non-alcoholic Fatty Liver Disease Pathogenesis.

Mazzoccoli G, De Cosmo S, Mazza T Front Physiol. 2018; 9:193.

PMID: 29662454 PMC: 5890189. DOI: 10.3389/fphys.2018.00193.

References

Fu Y, Zhong H, Wang M, Luo D, Liao H, Maeda H . Intrinsically photosensitive retinal ganglion cells detect light with a vitamin A-based photopigment, melanopsin. Proc Natl Acad Sci U S A. 2005; 102(29):10339-44. PMC: 1177370. DOI: 10.1073/pnas.0501866102. View

Bass J, Takahashi J . Circadian integration of metabolism and energetics. Science. 2010; 330(6009):1349-54. PMC: 3756146. DOI: 10.1126/science.1195027. View

REPA J, Turley S, Lobaccaro J, Medina J, Li L, Lustig K . Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers. Science. 2000; 289(5484):1524-9. DOI: 10.1126/science.289.5484.1524. View

Mangelsdorf D, Evans R . The RXR heterodimers and orphan receptors. Cell. 1995; 83(6):841-50. DOI: 10.1016/0092-8674(95)90200-7. View

Lin B, Wong C, Chen H, Privalsky M . Plasticity of tetramer formation by retinoid X receptors. An alternative paradigm for DNA recognition. J Biol Chem. 1997; 272(15):9860-7. DOI: 10.1074/jbc.272.15.9860. View

LeBlanc B, Stunnenberg H . 9-cis retinoic acid signaling: changing partners causes some excitement. Genes Dev. 1995; 9(15):1811-6. DOI: 10.1101/gad.9.15.1811. View

Dominguez M, Alvarez S, de Lera A . Natural and Structure-based RXR Ligand Scaffolds and Their Functions. Curr Top Med Chem. 2016; 17(6):631-662. DOI: 10.2174/1568026616666160617072521. View

Nakahata Y, Kaluzova M, Grimaldi B, Sahar S, Hirayama J, Chen D . The NAD+-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control. Cell. 2008; 134(2):329-40. PMC: 3526943. DOI: 10.1016/j.cell.2008.07.002. View

Thompson C, Selby C, Van Gelder R, Blaner W, Lee J, Quadro L . Effect of vitamin A depletion on nonvisual phototransduction pathways in cryptochromeless mice. J Biol Rhythms. 2004; 19(6):504-17. DOI: 10.1177/0748730404270519. View

10.

Yamada K, Kawata H, Shou Z, Mizutani T, Noguchi T, Miyamoto K . Insulin induces the expression of the SHARP-2/Stra13/DEC1 gene via a phosphoinositide 3-kinase pathway. J Biol Chem. 2003; 278(33):30719-24. DOI: 10.1074/jbc.M301597200. View

11.

Wan Y, An D, Cai Y, REPA J, Flores M, Postic C . Hepatocyte-specific mutation establishes retinoid X receptor alpha as a heterodimeric integrator of multiple physiological processes in the liver. Mol Cell Biol. 2000; 20(12):4436-44. PMC: 85811. DOI: 10.1128/MCB.20.12.4436-4444.2000. View

12.

L Bookout A, Jeong Y, Downes M, Yu R, Evans R, Mangelsdorf D . Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional network. Cell. 2006; 126(4):789-99. PMC: 6211849. DOI: 10.1016/j.cell.2006.06.049. View

13.

Nakahata Y, Akashi M, Trcka D, Yasuda A, Takumi T . The in vitro real-time oscillation monitoring system identifies potential entrainment factors for circadian clocks. BMC Mol Biol. 2006; 7:5. PMC: 1386696. DOI: 10.1186/1471-2199-7-5. View

14.

Finck B, Gropler M, Chen Z, Leone T, Croce M, Harris T . Lipin 1 is an inducible amplifier of the hepatic PGC-1alpha/PPARalpha regulatory pathway. Cell Metab. 2006; 4(3):199-210. DOI: 10.1016/j.cmet.2006.08.005. View

15.

Nakamura K, Inoue I, Takahashi S, Komoda T, Katayama S . Cryptochrome and Period Proteins Are Regulated by the CLOCK/BMAL1 Gene: Crosstalk between the PPARs/RXRalpha-Regulated and CLOCK/BMAL1-Regulated Systems. PPAR Res. 2008; 2008:348610. PMC: 2248703. DOI: 10.1155/2008/348610. View

16.

Liu C, Li S, Liu T, Borjigin J, Lin J . Transcriptional coactivator PGC-1alpha integrates the mammalian clock and energy metabolism. Nature. 2007; 447(7143):477-81. DOI: 10.1038/nature05767. View

17.

Chawla A, REPA J, Evans R, Mangelsdorf D . Nuclear receptors and lipid physiology: opening the X-files. Science. 2001; 294(5548):1866-70. DOI: 10.1126/science.294.5548.1866. View

18.

Zhao Y, Qin S, Atangan L, Molina Y, Okawa Y, Arpawong H . Casein kinase 1alpha interacts with retinoid X receptor and interferes with agonist-induced apoptosis. J Biol Chem. 2004; 279(29):30844-9. DOI: 10.1074/jbc.M404651200. View

19.

Yang X, Downes M, Yu R, L Bookout A, He W, Straume M . Nuclear receptor expression links the circadian clock to metabolism. Cell. 2006; 126(4):801-10. DOI: 10.1016/j.cell.2006.06.050. View

20.

Moschetta A . Nuclear receptors and cholesterol metabolism in the intestine. Atheroscler Suppl. 2015; 17:9-11. DOI: 10.1016/S1567-5688(15)50003-2. View