CRH-R2 signalling modulates feeding and circadian gene expression in hypothalamic mHypoA-2/30 neurons
File(s)
Published version
Author(s)
Alcantara-Alonso, Viridiana
Dallmann, Robert
Lehnert, Hendrik
de Gortari, Patricia
Grammatopoulos, Dimitris K
Type
Journal Article
Abstract
The hypothalamic type 2 corticotropin releasing hormone receptor (CRH-R2) plays critical roles in homeostatic regulation, particularly in fine tuning stress recovery. During acute stress, the CRH-R2 ligands CRH and urocortins promote adaptive responses and feeding inhibition. However, in rodent models of chronic stress, over-exposure of hypothalamic CRH-R2 to its cognate agonists is associated with urocortin 2 (Ucn2) resistance; attenuated cAMP-response element binding protein (CREB) phosphorylation and increased food intake. The molecular mechanisms involved in these altered CRH-R2 signalling responses are not well described. In the present study, we used the adult mouse hypothalamus-derived cell line mHypoA-2/30 to investigate CRH-R2 signalling characteristics focusing on gene expression of molecules involved in feeding and circadian regulation given the role of clock genes in metabolic control. We identified functional CRH-R2 receptors expressed in mHypoA-2/30 cells that differentially regulate CREB and AMP-activated protein kinase (AMPK) phosphorylation and downstream expression of the appetite-regulatory genes proopiomelanocortin (Pomc) and neuropeptide Y (Npy) in accordance with an anorexigenic effect. We studied for the first time the effects of Ucn2 on clock genes in native and in a circadian bioluminescence reporter expressing mHypoA-2/30 cells, detecting enhancing effects of Ucn2 on mRNA levels and rhythm amplitude of the circadian regulator Aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1), which could facilitate anorexic responses in the activity circadian phase. These data uncover novel aspects of CRH-R2 hypothalamic signalling that might be important in regulation of circadian feeding during stress responses.
Date Issued
2023-10-11
Date Acceptance
2023-09-13
Citation
Frontiers in Endocrinology, 2023, 14
ISSN
1664-2392
Publisher
Frontiers Media S.A.
Journal / Book Title
Frontiers in Endocrinology
Volume
14
Copyright Statement
© 2023 Alca´ntara-Alonso, Dallmann, Lehnert, de Gortari and Grammatopoulos. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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Subjects
AMPK
BRAIN
circadian rhythm
CORTICOTROPIN-RELEASING-HORMONE
CREB
CRH-R2
ELEMENT-BINDING PROTEIN
Endocrinology & Metabolism
Feeding
FOOD-INTAKE
HIGH-FAT DIET
hypothalamic peptides
LEPTIN
Life Sciences & Biomedicine
MESSENGER-RNA
RECEPTORS
Science & Technology
TRANSCRIPTION
UROCORTIN 2
urocortin 2 (UCN2)
Publication Status
Published
Article Number
1266081
Date Publish Online
2023-10-11