Aryl hydrocarbon receptor affects circadian-regulated lipolysis through an E-Box-dependent mechanism.
Journal
Molecular and cellular endocrinology
ISSN: 1872-8057
Titre abrégé: Mol Cell Endocrinol
Pays: Ireland
ID NLM: 7500844
Informations de publication
Date de publication:
01 01 2023
01 01 2023
Historique:
received:
10
08
2022
revised:
17
10
2022
accepted:
19
10
2022
pmc-release:
01
01
2024
pubmed:
26
10
2022
medline:
23
11
2022
entrez:
25
10
2022
Statut:
ppublish
Résumé
An internal circadian clock regulates timing of systemic energy homeostasis. The central clock in the hypothalamic suprachiasmatic nucleus (SCN) directs local clocks in peripheral tissues such as liver, muscle, and adipose tissue to synchronize metabolism with food intake and rest/activity cycles. Aryl hydrocarbon receptor (AhR) interacts with the molecular circadian clockworks. Activation of AhR dampens rhythmic expression of core clock genes, which may lead to metabolic dysfunction. Given the importance of appropriately-timed adipose tissue function to regulation of energy homeostasis, this study focused on mechanisms by which AhR may influence clock-controlled adipose tissue activity. We hypothesized that AhR activation in adipose tissue would impair lipolysis by dampening adipose rhythms, leading to a decreased lipolysis rate during fasting, and subsequently, altered serum glucose concentrations. Levels of clock gene and lipolysis gene transcripts in mouse mesenchymal stem cells (BMSCs) differentiated into mature adipocytes were suppressed by the AhR agonist β-napthoflavone (BNF), in an AhR dependent manner. BNF altered rhythms of core clock gene and lipolysis gene transcripts in C57bl6/J mice. BNF reduced serum free fatty acids, glycerol and liver glycogen. Chromatin immunoprecipitation indicated that BNF increased binding of AhR to E-Box elements in clock gene and lipolysis gene promoters. These data establish a link between AhR activation and impaired lipolysis, specifically by altering adipose tissue rhythmicity. In response to the decreased available energy from impaired lipolysis, the body increases glycogenolysis, thereby degrading more glycogen to provide necessary energy.
Identifiants
pubmed: 36283500
pii: S0303-7207(22)00257-X
doi: 10.1016/j.mce.2022.111809
pmc: PMC10509633
mid: NIHMS1928678
pii:
doi:
Substances chimiques
Receptors, Aryl Hydrocarbon
0
CLOCK Proteins
EC 2.3.1.48
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
111809Subventions
Organisme : NIEHS NIH HHS
ID : R15 ES030556
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest None.
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