CRH-R2 signalling modulates feeding and circadian gene expression in hypothalamic mHypoA-2/30 neurons
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 mode...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1266081/full |
| _version_ | 1797661945767133184 |
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| author | Viridiana Alcántara-Alonso Viridiana Alcántara-Alonso Robert Dallmann Hendrik Lehnert Patricia de Gortari Dimitris K. Grammatopoulos Dimitris K. Grammatopoulos |
| author_facet | Viridiana Alcántara-Alonso Viridiana Alcántara-Alonso Robert Dallmann Hendrik Lehnert Patricia de Gortari Dimitris K. Grammatopoulos Dimitris K. Grammatopoulos |
| author_sort | Viridiana Alcántara-Alonso |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T18:52:55Z |
| format | Article |
| id | doaj.art-b7eead883b35470fb22c17ecd9162252 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-03-11T18:52:55Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-b7eead883b35470fb22c17ecd91622522023-10-11T07:53:23ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-10-011410.3389/fendo.2023.12660811266081CRH-R2 signalling modulates feeding and circadian gene expression in hypothalamic mHypoA-2/30 neuronsViridiana Alcántara-Alonso0Viridiana Alcántara-Alonso1Robert Dallmann2Hendrik Lehnert3Patricia de Gortari4Dimitris K. Grammatopoulos5Dimitris K. Grammatopoulos6Translational Medicine, Warwick Medical School, University of Warwick, Coventry, United KingdomLaboratorio de Neurofisiología Molecular, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Ciudad de México, MexicoTranslational Medicine, Warwick Medical School, University of Warwick, Coventry, United KingdomRectorate, Paris Lodron Universität Salzburg, Salzburg, AustriaLaboratorio de Neurofisiología Molecular, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Ciudad de México, MexicoTranslational Medicine, Warwick Medical School, University of Warwick, Coventry, United KingdomInstitute of Precision Diagnostics and Translational Medicine, Pathology, University Hospital Coventry and Warwickshire (UHCW), National Health Service (NHS) Trust, Coventry, United KingdomThe 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.https://www.frontiersin.org/articles/10.3389/fendo.2023.1266081/fullFeedinghypothalamic peptidesCRH-R2urocortin 2 (UCN2)AMPKCREB |
| spellingShingle | Viridiana Alcántara-Alonso Viridiana Alcántara-Alonso Robert Dallmann Hendrik Lehnert Patricia de Gortari Dimitris K. Grammatopoulos Dimitris K. Grammatopoulos CRH-R2 signalling modulates feeding and circadian gene expression in hypothalamic mHypoA-2/30 neurons Frontiers in Endocrinology Feeding hypothalamic peptides CRH-R2 urocortin 2 (UCN2) AMPK CREB |
| title | CRH-R2 signalling modulates feeding and circadian gene expression in hypothalamic mHypoA-2/30 neurons |
| title_full | CRH-R2 signalling modulates feeding and circadian gene expression in hypothalamic mHypoA-2/30 neurons |
| title_fullStr | CRH-R2 signalling modulates feeding and circadian gene expression in hypothalamic mHypoA-2/30 neurons |
| title_full_unstemmed | CRH-R2 signalling modulates feeding and circadian gene expression in hypothalamic mHypoA-2/30 neurons |
| title_short | CRH-R2 signalling modulates feeding and circadian gene expression in hypothalamic mHypoA-2/30 neurons |
| title_sort | crh r2 signalling modulates feeding and circadian gene expression in hypothalamic mhypoa 2 30 neurons |
| topic | Feeding hypothalamic peptides CRH-R2 urocortin 2 (UCN2) AMPK CREB |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1266081/full |
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