Neuregulin 4 Is a Novel Marker of Beige Adipocyte Precursor Cells in Human Adipose Tissue
dc.contributor.author
dc.date.accessioned
2019-11-20T11:08:41Z
dc.date.available
2019-11-20T11:08:41Z
dc.date.issued
2019-01-31
dc.identifier.uri
dc.description.abstract
Nrg4 expression has been linked to brown adipose tissue activity and browning of white adipocytes in mice. Here, we aimed to investigate whether these observations could be translated to humans by investigating NRG4 mRNA and markers of brown/beige adipocytes in human visceral (VAT) and subcutaneous adipose tissue (SAT). We also studied the possible association of NRG4 with insulin action.
Methods: SAT and VAT NRG4 and markers of brown/beige (UCP1, UCP3, and TMEM26)-related gene expression were analyzed in two independent cohorts (n = 331 and n = 59). Insulin resistance/sensitivity was measured using HOMAIR and glucose infusion rate during euglycemic hyperinsulinemic clamp.
Results: In both cohort 1 and cohort 2, NRG4 and thermogenic/beige-related gene expression were significantly increased in VAT compared to SAT. Adipogenic-related genes followed an opposite pattern. In cohort 1, VAT NRG4 gene expression was positively correlated with BMI and expression of UCP1, UCP3, TMEM26, and negatively with adipogenic (FASN, PPARG, and SLC2A4)- and inflammatory (IL6 and IL8)-related genes. In SAT, NRG4 gene expression was negatively correlated with HOMAIR and positively with UCP1 and TMEM26 gene expression. Multiple linear regression analysis revealed that expression of TMEM26 gene was the best predictor of NRG4 gene expression in both VAT and SAT. Specifically, NRG4 and TMEM26 gene expression was significantly increased in VAT, but not in SAT stromal vascular fraction cells (p < 0.001). In cohort 2, the significant association between NRG4 and TMEM26 gene expression in both VAT and SAT was confirmed, and SAT NRG4 gene expression also was positively correlated with insulin action and the expression of UCP1.
Conclusion: Current findings suggest NRG4 gene expression as a novel marker of beige adipocytes in human adipose tissue
dc.description.sponsorship
This work was partially supported by research grants PI16/01173 from the Instituto de Salud Carlos III from Spain, FEDER funds and by Fundació Marató de TV3 (201626-30). CIBEROBN Fisiopatología de la Obesidad y Nutrición is an initiative from the Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional (FEDER) from Spain
dc.format.mimetype
application/pdf
dc.language.iso
eng
dc.publisher
Frontiers Media
dc.relation.isformatof
Reproducció digital del document publicat a: https://doi.org/10.3389/fphys.2019.00039
dc.relation.ispartof
Frontiers in Physiology, 2019, vol. 10, art. núm. 39
dc.relation.ispartofseries
Articles publicats (D-CM)
dc.rights
Attribution 4.0 International
dc.rights.uri
dc.title
Neuregulin 4 Is a Novel Marker of Beige Adipocyte Precursor Cells in Human Adipose Tissue
dc.type
info:eu-repo/semantics/article
dc.rights.accessRights
info:eu-repo/semantics/openAccess
dc.type.version
info:eu-repo/semantics/publishedVersion
dc.identifier.doi
dc.identifier.idgrec
030193
dc.type.peerreviewed
peer-reviewed
dc.identifier.eissn
1664-042X