ArticleThe Journal of biological chemistry2016
Hepatic Aryl Hydrocarbon Receptor Attenuates Fibroblast Growth Factor 21 Expression.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- Glucose and lipopolysaccharide differentially regulate fibroblast growth factor 21 in healthy male human volunteers - A prospective cross-over trial.Journal of cellular and molecular medicine · 2022Trial
- Perfluorooctane sulfonate (PFOS) interferes with Cyp1a activity and dysregulates the aryl hydrocarbon receptor pathway in larval zebrafish (Danio rerio).Environmental pollution (Barking, Essex : 1987) · 2026Article
- Molecular mechanisms of dose-dependent regulation of hepatic lipid metabolism by BaP through modulation of AhR binding to XRE1 or XRE3.Frontiers in pharmacology · 2025Article
- Aryl hydrocarbon receptor (AhR)-mediated signaling as a critical regulator of skeletal cell biology.Journal of molecular endocrinology · 2022Review
- Sexual Dimorphism in Adipose-Hypothalamic Crosstalk and the Contribution of Aryl Hydrocarbon Receptor to Regulate Energy Homeostasis.International journal of molecular sciences · 2022Review
- Bilirubin as a metabolic hormone: the physiological relevance of low levels.American journal of physiology. Endocrinology and metabolism · 2021Review
- Nutritional Regulation of Hepatic FGF21 by Dietary Restriction of Methionine.Frontiers in endocrinology · 2021Review
- FGF21 serum levels are related to insulin resistance, metabolic changes and obesity in Mexican people living with HIV (PLWH).PloS one · 2021Article
- The Aryl Hydrocarbon Receptor in Energy Balance: The Road from Dioxin-Induced Wasting Syndrome to Combating Obesity with Ahr Ligands.International journal of molecular sciences · 2020Review
- The sulfate metabolite of 3,3'-dichlorobiphenyl (PCB-11) impairs Cyp1a activity and increases hepatic neutral lipids in zebrafish larvae (Danio rerio).Chemosphere · 2020Article
- Article
- Microbiota Metabolism Promotes Synthesis of the Human Ah Receptor Agonist 2,8-Dihydroxyquinoline.Journal of proteome research · 2019Article
- Inducible Loss of the Aryl Hydrocarbon Receptor Activates Perigonadal White Fat Respiration and Brown Fat Thermogenesis via Fibroblast Growth Factor 21.International journal of molecular sciences · 2019Article
- Polychlorinated biphenyl exposures differentially regulate hepatic metabolism and pancreatic function: Implications for nonalcoholic steatohepatitis and diabetes.Toxicology and applied pharmacology · 2019Article
- The role of hypoxia-inducible factors in metabolic diseases.Nature reviews. Endocrinology · 2018Review
- The Biological Clock: A Pivotal Hub in Non-alcoholic Fatty Liver Disease Pathogenesis.Frontiers in physiology · 2018Review
- A Specific ChREBP and PPARα Cross-Talk Is Required for the Glucose-Mediated FGF21 Response.Cell reports · 2017Article
- Emerging roles of xenobiotic detoxification enzymes in metabolic diseases.Reviews on environmental health · 2017Review
- Dose-Dependent Metabolic Reprogramming and Differential Gene Expression in TCDD-Elicited Hepatic Fibrosis.Toxicological sciences : an official journal of the Society of Toxicology · 2016Article
- Role of Aryl Hydrocarbon Receptor in Circadian Clock Disruption and Metabolic Dysfunction.Environmental health insights · 2016Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor involved in many physiological processes. Several studies indicate that AHR is also involved in energy homeostasis. Fibroblast growth factor 21 (FGF21) is an important regulator of the fasting and feeding responses. When administered to various genetic and diet-induced mouse models of obesity, FGF21 can attenuate obesity-associated morbidities. Here, we explore the role of AHR in hepatic Fgf21 expression through the use of a conditional, hepatocyte-targeted AHR knock-out mouse model (Cre(Alb)Ahr(Fx/Fx)). Compared with the congenic parental strain (Ahr(Fx/Fx)), non-fasted Cre(Alb)Ahr(Fx/Fx) mice exhibit a 4-fold increase in hepatic Fgf21 expression, as well as elevated expression of the FGF21-target gene Igfbp1 Furthermore, in vivo agonist activation of AHR reduces hepatic Fgf21 expression during a fast. The Fgf21 promoter contains several putative dioxin response elements (DREs). Using EMSA, we demonstrate that the AHR-ARNT heterodimer binds to a specific DRE that overlaps binding sequences for peroxisome proliferator-activated receptor α (PPARα), carbohydrate response element-binding protein (ChREBP), and cAMP response element-binding protein, hepatocyte specific (CREBH). In addition, we reveal that agonist-activated AHR impairs PPARα-, ChREBP-, and CREBH-mediated promoter activity in Hepa-1 cells. Accordingly, agonist treatment in Hepa-1 cells ablates potent ER stress-driven Fgf21 expression, and pre-treatment with AHR antagonist blocks this effect. Finally, we show that pre-treatment of primary human hepatocytes with AHR agonist diminishes PPARα-, glucose-, and ER stress-driven induction of FGF21 expression, indicating the effect is not mouse-specific. Together, our data show that AHR contributes to hepatic energy homeostasis, partly through the regulation of FGF21 expression and signaling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.