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Deletion of iRhom2 protects against diet-induced obesity by increasing thermogenesis

2020Journal article Open access
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dc.contributor.authorBadenes, Marina
dc.contributor.authorAmin, Abdulbasit
dc.contributor.authorGonzález-García, Ismael
dc.contributor.authorFélix, Inês
dc.contributor.authorBurbridge, Emma
dc.contributor.authorCavadas, Miguel
dc.contributor.authorOrtega, Francisco José
dc.contributor.authorde Carvalho, Érika
dc.contributor.authorFaísca, Pedro
dc.contributor.authorCarobbio, Stefania
dc.contributor.authorSeixas, Elsa
dc.contributor.authorPedroso, Dora
dc.contributor.authorNeves-Costa, Ana
dc.contributor.authorMoita, Luís F.
dc.contributor.authorFernández-Real, José Manuel
dc.contributor.authorVidal-Puig, António
dc.contributor.authorDomingos, Ana
dc.contributor.authorLópez, Miguel
dc.contributor.authorAdrain, Colin
dc.date.accessioned2019-12-09T23:09:49Z
dc.date.available2019-12-09T23:09:49Z
dc.date.issued2020
dc.description.abstractObjective: Obesity is the result of positive energy balance. It can be caused by excessive energy consumption but also by decreased energy dissipation, which occurs under several conditions including when the development or activation of brown adipose tissue (BAT) is impaired. Here we evaluated whether iRhom2, the essential cofactor for the Tumour Necrosis Factor (TNF) sheddase ADAM17/TACE, plays a role in the pathophysiology of metabolic syndrome. Methods: We challenged WT versus iRhom2 KO mice to positive energy balance by chronic exposure to a high fat diet and then compared their metabolic phenotypes. We also carried out ex vivo assays with primary and immortalized mouse brown adipocytes to establish the autonomy of the effect of loss of iRhom2 on thermogenesis and respiration. Results: Deletion of iRhom2 protected mice from weight gain, dyslipidemia, adipose tissue inflammation, and hepatic steatosis and improved insulin sensitivity when challenged by a high fat diet. Crucially, the loss of iRhom2 promotes thermogenesis via BAT activation and beige adipocyte recruitment, enabling iRhom2 KO mice to dissipate excess energy more efficiently than WT animals. This effect on enhanced ther- mogenesis is cell-autonomous in brown adipocytes as iRhom2 KOs exhibit elevated UCP1 levels and increased mitochondrial proton leak.pt_PT
dc.description.abstractConclusion:Our data suggest that iRhom2 is a negative regulator of thermogenesis and plays a role in the control of adipose tissue homeostasis during metabolic disease.pt_PT
dc.description.versioninfo:eu-repo/semantics/acceptedVersionpt_PT
dc.identifier.doi10.1016/j.molmet.2019.10.006pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.7/910
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevier GmbHpt_PT
dc.relationFCT, SFRH/BCC/52507/2014; PTDC/BEX- BCM/3015/2014; LISBOA-01e0145-FEDER-031330pt_PT
dc.relationCell signaling control: mechanisms of TACE regulation during EGFR transactivation
dc.relationFCT: PTDC/BIM-MEC/4665/2014pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectiRhom2; ADAM17/TACEpt_PT
dc.subjectObesitypt_PT
dc.subjectInsulin resistancept_PT
dc.subjectNAFLDpt_PT
dc.subjectBATpt_PT
dc.subjectBrowningpt_PT
dc.subjectThermogenesispt_PT
dc.subjectUCP1pt_PT
dc.titleDeletion of iRhom2 protects against diet-induced obesity by increasing thermogenesispt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleCell signaling control: mechanisms of TACE regulation during EGFR transactivation
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/SFRH%2FBPD%2F117216%2F2016/PT
oaire.citation.endPage84pt_PT
oaire.citation.startPage67pt_PT
oaire.citation.titleMolecular Metabolismpt_PT
oaire.citation.volume31pt_PT
oaire.fundingStreamOE
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication40ca9a09-f920-4413-8bab-19bc393424fe
relation.isProjectOfPublication.latestForDiscovery40ca9a09-f920-4413-8bab-19bc393424fe

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