Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/104799
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dc.contributor.authorTeodoro, João S.-
dc.contributor.authorMachado, Ivo F.-
dc.contributor.authorCastela, Ana C.-
dc.contributor.authorAmorim, João A.-
dc.contributor.authorJarak, Ivana-
dc.contributor.authorCarvalho, Rui A.-
dc.contributor.authorPalmeira, Carlos M.-
dc.contributor.authorRolo, Anabela P.-
dc.date.accessioned2023-01-25T09:45:43Z-
dc.date.available2023-01-25T09:45:43Z-
dc.date.issued2021-10-29-
dc.identifier.issn1422-0067pt
dc.identifier.urihttps://hdl.handle.net/10316/104799-
dc.description.abstractBile acids (BA) have shown promising effects in animal models of obesity. However, the said effects are thought to rely on a thermogenic effect, which is questionably present in humans. A previous work has shown that the BA chenodeoxycholic acid (CDCA) can revert obesity and accelerate metabolism in animal and cell culture models. Thus, the aim of this study was to understand if this obesity reduction is indeed thermogenically-dependent. A CRISPR/Cas9 model of TGR5 (BA receptor) knockdown in 3T3-L1 adipocytes was developed to diminish thermogenic effects. Various parameters were assessed, including mitochondrial bioenergetics by Seahorse flux analysis, oxidative stress and membrane potential by fluorometry, intermediary metabolism by NMR, protein content assessment by Western Blot, gene expression by qPCR, and confocal microscopy evaluation of mitophagy. CDCA was still capable, for the most part, of reversing the harmful effects of cellular obesity, elevating mitophagy and leading to the reduction of harmed mitochondria within the cells, boosting mitochondrial activity, and thus energy consumption. In summary, CDCA has a non-thermogenic, obesity reducing capacity that hinges on a healthy mitochondrial population, explaining at least some of these effects and opening avenues of human treatment for metabolic diseases.pt
dc.language.isoengpt
dc.publisherMDPIpt
dc.relationUIDB/04539/2020pt
dc.relationUIDP/04539/2020pt
dc.relationSFRH/BPD/94036/2013pt
dc.relationCEECIND/4400/2017pt
dc.relationHEALTHYAGING 2020 CENTRO-01-0145- FEDER-000012pt
dc.relationFCT - PhD scholarship (PD/BD/114173/2016)pt
dc.rightsopenAccesspt
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt
dc.subjectCDCApt
dc.subjectTGR5pt
dc.subjectmitochondriapt
dc.subjectmitophagypt
dc.subjectCRISPR/Cas9pt
dc.subject3T3-L1pt
dc.subject.mesh3T3-L1 Cellspt
dc.subject.meshAnimalspt
dc.subject.meshAnti-Obesity Agentspt
dc.subject.meshChenodeoxycholic Acidpt
dc.subject.meshGene Knockdown Techniquespt
dc.subject.meshMicept
dc.subject.meshMitochondriapt
dc.subject.meshObesitypt
dc.subject.meshReceptors, G-Protein-Coupledpt
dc.subject.meshThermogenesispt
dc.subject.meshCRISPR-Cas Systemspt
dc.titleChenodeoxycholic Acid Has Non-Thermogenic, Mitodynamic Anti-Obesity Effects in an In Vitro CRISPR/Cas9 Model of Bile Acid Receptor TGR5 Knockdownpt
dc.typearticle-
degois.publication.firstPage11738pt
degois.publication.issue21pt
degois.publication.titleInternational Journal of Molecular Sciencespt
dc.peerreviewedyespt
dc.identifier.doi10.3390/ijms222111738pt
degois.publication.volume22pt
dc.date.embargo2021-10-29*
uc.date.periodoEmbargo0pt
item.fulltextCom Texto completo-
item.cerifentitytypePublications-
item.languageiso639-1en-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.grantfulltextopen-
item.openairetypearticle-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.orcid0000-0002-1244-275X-
crisitem.author.orcid0000-0002-9666-4594-
crisitem.author.orcid0000-0002-0129-4114-
crisitem.author.orcid0000-0003-1820-0353-
crisitem.author.orcid0000-0002-2639-7697-
crisitem.author.orcid0000-0003-3535-9630-
Appears in Collections:FCTUC Ciências da Vida - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais
IIIUC - Artigos em Revistas Internacionais
FFUC- Artigos em Revistas Internacionais
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