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Opposing Actions of TLR2 and TLR4 in Adipocyte Differentiation and Mature-Onset Obesity

dc.contributor.authorCuesta Rubio, Natalia
dc.contributor.authorFernández-Veledo, Sonia
dc.contributor.authorPunzón, Carmen
dc.contributor.authorMoreno, Cristóbal
dc.contributor.authorBarrocal, Beatriz
dc.contributor.authorSreeramkumar, Vinatha
dc.contributor.authorDesco, Manuel
dc.contributor.authorFresno, Manuel
dc.date.accessioned2023-06-22T12:35:27Z
dc.date.available2023-06-22T12:35:27Z
dc.date.issued2022-12-10
dc.description.abstractUnderstanding the signaling cascades that govern adipocyte metabolism and differentiation is necessary for the development of therapies for obesity. Toll-like receptors (TLRs) are key mediators in adipogenesis, but their specific role is not completely understood. In this study, siRNA knockdown of Tlr2 in 3T3-L1 cells allowed them to differentiate more efficiently into adipocytes, whereas the opposite was observed for the knockdown of Tlr4. At the same time, we show that TLR2 knock-out mice spontaneously developed mature-onset obesity and insulin resistance. Besides a higher incidence of hyperplasia and hypertrophy in white adipose tissue (WAT), we found a significantly increased number of adipocyte precursor cells in TLR2-/- mice compared to TLR4-/- mice. Interestingly, genetic inactivation of Tlr4 in TLR2-/- mice reverted their increased adiposity, insulin resistance, and restored normal levels of adipocyte precursor cells. These findings provide evidence that TLR2 and TLR4 play opposing roles in WAT homeostasis and point to the existence of cross-regulation among TLR2 and TLR4 during adipocyte differentiation both in vitro and in vivo.
dc.description.departmentSección Deptal. de Biología Celular (Medicina)
dc.description.facultyFac. de Medicina
dc.description.refereedTRUE
dc.description.sponsorshipUnión Europea. Horizonte 2020
dc.description.sponsorshipMinisterio de Ciencia e Innovacion (MICINN)
dc.description.sponsorshipComunidad de Madrid
dc.description.statuspub
dc.eprint.idhttps://eprints.ucm.es/id/eprint/76415
dc.identifier.doi10.3390/ijms232415682
dc.identifier.issn1422-0067
dc.identifier.officialurlhttps://www.mdpi.com/1422-0067/23/24/15682
dc.identifier.urihttps://hdl.handle.net/20.500.14352/72889
dc.issue.number23
dc.journal.titleInternational Journal of Molecular Sciences
dc.language.isoeng
dc.page.initial15682
dc.publisherMDPI
dc.relation.projectIDTOLLerant (642157)
dc.relation.projectIDSAF2010-18733; SAF2016-75988-R
dc.relation.projectIDINFLAMUNE-CM (S2017/BMD-3671)
dc.rights.accessRightsopen access
dc.subject.cdu576
dc.subject.cdu577
dc.subject.keywordObesidad
dc.subject.keywordTLR2
dc.subject.keywordTLR4
dc.subject.keywordObesity
dc.subject.ucmBiología
dc.subject.ucmBiología celular (Biología)
dc.subject.ucmBiología molecular (Biología)
dc.subject.unesco24 Ciencias de la Vida
dc.subject.unesco2407 Biología Celular
dc.subject.unesco2415 Biología Molecular
dc.titleOpposing Actions of TLR2 and TLR4 in Adipocyte Differentiation and Mature-Onset Obesity
dc.typejournal article
dc.volume.number24
dspace.entity.typePublication
relation.isAuthorOfPublication5be9c770-1f19-4bc8-bfb1-5227dcf3c656
relation.isAuthorOfPublication.latestForDiscovery5be9c770-1f19-4bc8-bfb1-5227dcf3c656

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