RNA-seq reveals that anti-obesity irisin and triiodothyronine (T3) hormones differentially affect the purinergic signaling transcriptomics in differentiated human adipocytes

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dc.contributor.authorMathias, Lucas Solla [UNESP]
dc.contributor.authorHerman-de-Sousa, Carina
dc.contributor.authorCury, Sarah Santiloni [UNESP]
dc.contributor.authorNogueira, Célia Regina [UNESP]
dc.contributor.authorCorreia-de-Sá, Paulo
dc.contributor.authorde Oliveira, Miriane [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.contributor.institutionUniversidade do Porto (ICBAS-UP)
dc.contributor.institutionICBAS-UP
dc.date.accessioned2023-07-29T16:03:31Z
dc.date.available2023-07-29T16:03:31Z
dc.date.issued2023-04-01
dc.description.abstractThe anti-obesity thyroid hormone, triiodothyronine (T3), and irisin, an exercise- and/or cold-induced myokine, stimulate thermogenesis and energy consumption while decreasing lipid accumulation. The involvement of ATP signaling in adipocyte cell function and obesity has attracted increasing attention, but the crosstalk between the purinergic signaling cascade and anti-obesity hormones lacks experimental evidence. In this study, we investigated the effects of T3 and irisin in the transcriptomics of membrane-bound purinoceptors, ectonucleotidase enzymes and nucleoside transporters participating in the purinergic signaling in cultured human adipocytes. The RNA-seq analysis revealed that differentiated adipocytes express high amounts of ADORA1, P2RY11, P2RY12, and P2RX6 gene transcripts, along with abundant levels of transcriptional products encoding to purine metabolizing enzymes (ENPP2, ENPP1, NT5E, ADA and ADK) and transporters (SLC29A1, SCL29A2). The transcriptomics of purinergic signaling markers changed in parallel to the upsurge of “browning” adipocyte markers, like UCP1 and P2RX5, after treatment with T3 and irisin. Upregulation of ADORA1, ADORA2A and P2RX4 gene transcription was obtained with irisin, whereas T3 preferentially upregulated NT5E, SLC29A2 and P2RY11 genes. Irisin was more powerful than T3 towards inhibition of the leptin gene transcription, the SCL29A1 gene encoding for the ENT1 transporter, the E-NPP2 (autotaxin) gene, and genes that encode for two ADP-sensitive P2Y receptors, P2RY1 and P2RY12. These findings indicate that anti-obesity irisin and T3 hormones differentially affect the purinergic signaling transcriptomics, which might point towards new directions for the treatment of obesity and related metabolic disorders that are worth to be pursued in future functional studies.en
dc.description.affiliationDepartment of Internal Clinic Botucatu Medical School São Paulo State University (UNESP), São Paulo
dc.description.affiliationLaboratório de Farmacologia e Neurobiologia Departamento de Imuno-Fisiologia e Farmacologia Instituto de Ciências Biomédicas de Abel Salazar Universidade do Porto (ICBAS-UP)
dc.description.affiliationCenter for Drug Discovery and Innovative Medicines (MedInUP) ICBAS-UP
dc.description.affiliationDepartment of Structural and Functional Biology Institute of Biosciences São Paulo State University (UNESP), São Paulo
dc.description.affiliationUnespDepartment of Internal Clinic Botucatu Medical School São Paulo State University (UNESP), São Paulo
dc.description.affiliationUnespDepartment of Structural and Functional Biology Institute of Biosciences São Paulo State University (UNESP), São Paulo
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipEuropean Social Fund
dc.description.sponsorshipFundação para a Ciência e a Tecnologia
dc.description.sponsorshipIdFAPESP: 2016/03242-3
dc.description.sponsorshipIdFAPESP: 2020/06763-0
dc.description.sponsorshipIdCNPq: 409438/2016
dc.description.sponsorshipIdEuropean Social Fund: NORTE-08-5369-FSE-000011
dc.description.sponsorshipIdFundação para a Ciência e a Tecnologia: UIDB/04308/2020
dc.identifierhttp://dx.doi.org/10.1016/j.bbalip.2022.159276
dc.identifier.citationBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, v. 1868, n. 4, 2023.
dc.identifier.doi10.1016/j.bbalip.2022.159276
dc.identifier.issn1879-2618
dc.identifier.issn1388-1981
dc.identifier.scopus2-s2.0-85146576762
dc.identifier.urihttp://hdl.handle.net/11449/249576
dc.language.isoeng
dc.relation.ispartofBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
dc.sourceScopus
dc.subjectAdenosine
dc.subjectATP
dc.subjectHuman adipocytes
dc.subjectIrisin
dc.subjectObesity
dc.subjectPurinergic signaling
dc.subjectThyroid hormones
dc.titleRNA-seq reveals that anti-obesity irisin and triiodothyronine (T3) hormones differentially affect the purinergic signaling transcriptomics in differentiated human adipocytesen
dc.typeArtigo
unesp.author.orcid0000-0002-6114-9189 0000-0002-6114-9189[5]

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