Next Article in Journal
Integrated Multi-Assay Culture Model for Stem Cell Chondrogenic Differentiation
Next Article in Special Issue
The Prognostic Impact of the Aryl Hydrocarbon Receptor (AhR) in Primary Breast Cancer Depends on the Lymph Node Status
Previous Article in Journal
Decoding the Mechanism of Action of Rapid-Acting Antidepressant Treatment Strategies: Does Gender Matter?
Previous Article in Special Issue
NAP Family CG5017 Chaperone Pleiotropically Regulates Human AHR Target Genes Expression in Drosophila Testis
Open AccessArticle

Inducible Loss of the Aryl Hydrocarbon Receptor Activates Perigonadal White Fat Respiration and Brown Fat Thermogenesis via Fibroblast Growth Factor 21

1
Department of Pharmacology and Toxicology, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA
2
Division of Surgical Sciences, Department of Surgery, UTMB & Metabolism Unit, Shriners Hospitals for Children, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA
3
Division of Rehabilitation Sciences, School of Health Professions, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA
4
Department of Internal Medicine, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(4), 950; https://doi.org/10.3390/ijms20040950
Received: 18 January 2019 / Revised: 14 February 2019 / Accepted: 19 February 2019 / Published: 22 February 2019
(This article belongs to the Special Issue Aryl Hydrocarbon Receptor in Biology and Toxicology)
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor highly expressed in hepatocytes. Researchers have employed global and liver-specific conditional Ahr knockout mouse models to characterize the physiological roles of the AHR; however, the gestational timing of AHR loss in these models can complicate efforts to distinguish the direct and indirect effects of post-gestational AHR deficiency. Utilizing a novel tamoxifen-inducible AHR knockout mouse model, we analyzed the effects of hepatocyte-targeted AHR loss in adult mice. The data demonstrate that AHR deficiency significantly reduces weight gain and adiposity, and increases multilocular lipid droplet formation within perigonadal white adipose tissue (gWAT). Protein and mRNA expression of fibroblast growth factor 21 (FGF21), an important hepatokine that activates thermogenesis in brown adipose tissue (BAT) and gWAT, significantly increases upon AHR loss and correlates with a significant increase of BAT and gWAT respiratory capacity. Confirming the role of FGF21 in mediating these effects, this phenotype is reversed in mice concomitantly lacking AHR and FGF21 expression. Chromatin immunoprecipitation analyses suggest that the AHR may constitutively suppress Fgf21 transcription through binding to a newly identified xenobiotic response element within the Fgf21 promoter. The data demonstrate an important AHR-FGF21 regulatory axis that influences adipose biology and may represent a “druggable” therapeutic target for obesity and its related metabolic disorders. View Full-Text
Keywords: aryl hydrocarbon receptor; fibroblast growth factor 21; uncoupling protein 1 aryl hydrocarbon receptor; fibroblast growth factor 21; uncoupling protein 1
Show Figures

Figure 1

MDPI and ACS Style

Girer, N.G.; Carter, D.; Bhattarai, N.; Mustafa, M.; Denner, L.; Porter, C.; Elferink, C.J. Inducible Loss of the Aryl Hydrocarbon Receptor Activates Perigonadal White Fat Respiration and Brown Fat Thermogenesis via Fibroblast Growth Factor 21. Int. J. Mol. Sci. 2019, 20, 950.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop