Gender-specific alteration of energy balance and circadian locomotor activity in the Crtc1 knockout mouse model of depression

Handle URI:
http://hdl.handle.net/10754/626373
Title:
Gender-specific alteration of energy balance and circadian locomotor activity in the Crtc1 knockout mouse model of depression
Authors:
Rossetti, Clara; Sciarra, Daniel; Petit, Jean-Marie; Eap, Chin B.; Halfon, Olivier; Magistretti, Pierre J. ( 0000-0002-6678-320X ) ; Boutrel, Benjamin ( 0000-0003-4988-759X ) ; Cardinaux, Jean-René ( 0000-0001-6423-0014 )
Abstract:
Obesity and depression are major public health concerns, and there is increasing evidence that they share etiological mechanisms. CREB-regulated transcription coactivator 1 (CRTC1) participates in neurobiological pathways involved in both mood and energy balance regulation. Crtc1 -/- mice rapidly develop a depressive-like and obese phenotype in early adulthood, and are therefore a relevant animal model to explore possible common mechanisms underlying mood disorders and obesity. Here, the obese phenotype of male and female Crtc1 -/- mice was further characterized by investigating CRTC1's role in the homeostatic and hedonic regulation of food intake, as well as its influence on daily locomotor activity. Crtc1 -/- mice showed a strong gender difference in the homeostatic regulation of energy balance. Mutant males were hyperphagic and rapidly developed obesity on normal chow diet, whereas Crtc1 -/- females exhibited mild late-onset obesity without hyperphagia. Overeating of mutant males was accompanied by alterations in the expression of several orexigenic and anorexigenic hypothalamic genes, thus confirming a key role of CRTC1 in the central regulation of food intake. No alteration in preference and conditioned response for saccharine was observed in Crtc1 -/- mice, suggesting that mutant males' hyperphagia was not due to an altered hedonic regulation of food intake. Intriguingly, mutant males exhibited a hyperphagic behavior only during the resting (diurnal) phase of the light cycle. This abnormal feeding behavior was associated with a higher diurnal locomotor activity indicating that the lack of CRTC1 may affect circadian rhythmicity. Collectively, these findings highlight the male-specific involvement of CRTC1 in the central control of energy balance and circadian locomotor activity.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division
Citation:
Rossetti C, Sciarra D, Petit J-M, Eap CB, Halfon O, et al. (2017) Gender-specific alteration of energy balance and circadian locomotor activity in the Crtc1 knockout mouse model of depression. Translational Psychiatry 7. Available: http://dx.doi.org/10.1038/s41398-017-0023-4.
Publisher:
Springer Nature
Journal:
Translational Psychiatry
Issue Date:
6-Dec-2017
DOI:
10.1038/s41398-017-0023-4
Type:
Article
ISSN:
2158-3188
Sponsors:
This work was partly funded by a grant from the Swiss National Science Foundation (31003A-135692), and supported by the National Centre of Competence in Research (NCCR) Synapsy.
Additional Links:
https://www.nature.com/articles/s41398-017-0023-4
Appears in Collections:
Articles; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorRossetti, Claraen
dc.contributor.authorSciarra, Danielen
dc.contributor.authorPetit, Jean-Marieen
dc.contributor.authorEap, Chin B.en
dc.contributor.authorHalfon, Olivieren
dc.contributor.authorMagistretti, Pierre J.en
dc.contributor.authorBoutrel, Benjaminen
dc.contributor.authorCardinaux, Jean-Renéen
dc.date.accessioned2017-12-14T12:34:04Z-
dc.date.available2017-12-14T12:34:04Z-
dc.date.issued2017-12-06en
dc.identifier.citationRossetti C, Sciarra D, Petit J-M, Eap CB, Halfon O, et al. (2017) Gender-specific alteration of energy balance and circadian locomotor activity in the Crtc1 knockout mouse model of depression. Translational Psychiatry 7. Available: http://dx.doi.org/10.1038/s41398-017-0023-4.en
dc.identifier.issn2158-3188en
dc.identifier.doi10.1038/s41398-017-0023-4en
dc.identifier.urihttp://hdl.handle.net/10754/626373-
dc.description.abstractObesity and depression are major public health concerns, and there is increasing evidence that they share etiological mechanisms. CREB-regulated transcription coactivator 1 (CRTC1) participates in neurobiological pathways involved in both mood and energy balance regulation. Crtc1 -/- mice rapidly develop a depressive-like and obese phenotype in early adulthood, and are therefore a relevant animal model to explore possible common mechanisms underlying mood disorders and obesity. Here, the obese phenotype of male and female Crtc1 -/- mice was further characterized by investigating CRTC1's role in the homeostatic and hedonic regulation of food intake, as well as its influence on daily locomotor activity. Crtc1 -/- mice showed a strong gender difference in the homeostatic regulation of energy balance. Mutant males were hyperphagic and rapidly developed obesity on normal chow diet, whereas Crtc1 -/- females exhibited mild late-onset obesity without hyperphagia. Overeating of mutant males was accompanied by alterations in the expression of several orexigenic and anorexigenic hypothalamic genes, thus confirming a key role of CRTC1 in the central regulation of food intake. No alteration in preference and conditioned response for saccharine was observed in Crtc1 -/- mice, suggesting that mutant males' hyperphagia was not due to an altered hedonic regulation of food intake. Intriguingly, mutant males exhibited a hyperphagic behavior only during the resting (diurnal) phase of the light cycle. This abnormal feeding behavior was associated with a higher diurnal locomotor activity indicating that the lack of CRTC1 may affect circadian rhythmicity. Collectively, these findings highlight the male-specific involvement of CRTC1 in the central control of energy balance and circadian locomotor activity.en
dc.description.sponsorshipThis work was partly funded by a grant from the Swiss National Science Foundation (31003A-135692), and supported by the National Centre of Competence in Research (NCCR) Synapsy.en
dc.publisherSpringer Natureen
dc.relation.urlhttps://www.nature.com/articles/s41398-017-0023-4en
dc.rightsThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleGender-specific alteration of energy balance and circadian locomotor activity in the Crtc1 knockout mouse model of depressionen
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.identifier.journalTranslational Psychiatryen
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionService of Child and Adolescent Psychiatry, Department of Psychiatry, University Medical Center, University of Lausanne, Lausanne, Switzerland.en
dc.contributor.institutionCenter for Psychiatric Neuroscience, Department of Psychiatry, University Medical Center, University of Lausanne, Prilly, Switzerland.en
dc.contributor.institutionLaboratory of Neuroenergetics and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.en
dc.contributor.institutionSchool of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland.en
kaust.authorMagistretti, Pierre J.en
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