HAND2 is a novel obesity-linked adipogenic transcription factor regulated by glucocorticoid signalling

  1. Giroud, Maude ORCID logo
  2. Tsokanos, Foivos-Filippos
  3. Caratti, Giorgio ORCID logo
  4. Kotschi, Stefan
  5. Khani, Sajjad ORCID logo
  6. Jouffe, Céline ORCID logo
  7. Vogl, Elena S.
  8. Irmler, Martin ORCID logo
  9. Glantschnig, Christina ORCID logo
  10. Gil Lozano, Manuel ORCID logo
  11. Hass, Daniela
  12. Ali Khan, Asrar ORCID logo
  13. Rios Garcia, Marcos ORCID logo
  14. Mattijssen, Frits
  15. Maida, Adriano
  16. Tews, Daniel ORCID logo
  17. Fischer-Posovszky, Pamela ORCID logo
  18. Feuchtinger, Annette ORCID logo
  19. Virtanen, Kirsi A.
  20. Beckers, Johannes
  21. WABITSCH, MARTIN ORCID logo
  22. Uhlenhaut, Henriette ORCID logo
  23. Blüher, Matthias ORCID logo
  24. Tuckermann, Jan ORCID logo
  25. Scheideler, Marcel ORCID logo
  26. Bartelt, Alexander ORCID logo
  27. Herzig, Stephan ORCID logo

Download
s00125-021-05470-y.pdf 1,60MB
WeightNameValue
1000 Titel
  • HAND2 is a novel obesity-linked adipogenic transcription factor regulated by glucocorticoid signalling
1000 Autor/in
  1. Giroud, Maude |
  2. Tsokanos, Foivos-Filippos |
  3. Caratti, Giorgio |
  4. Kotschi, Stefan |
  5. Khani, Sajjad |
  6. Jouffe, Céline |
  7. Vogl, Elena S. |
  8. Irmler, Martin |
  9. Glantschnig, Christina |
  10. Gil Lozano, Manuel |
  11. Hass, Daniela |
  12. Ali Khan, Asrar |
  13. Rios Garcia, Marcos |
  14. Mattijssen, Frits |
  15. Maida, Adriano |
  16. Tews, Daniel |
  17. Fischer-Posovszky, Pamela |
  18. Feuchtinger, Annette |
  19. Virtanen, Kirsi A. |
  20. Beckers, Johannes |
  21. WABITSCH, MARTIN |
  22. Uhlenhaut, Henriette |
  23. Blüher, Matthias |
  24. Tuckermann, Jan |
  25. Scheideler, Marcel |
  26. Bartelt, Alexander |
  27. Herzig, Stephan |
1000 Erscheinungsjahr 2021
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-05-20
1000 Erschienen in
1000 Quellenangabe
  • 64(8):1850-1865
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1007/s00125-021-05470-y |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245394/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Aims/hypothesis!#!Adipocytes are critical cornerstones of energy metabolism. While obesity-induced adipocyte dysfunction is associated with insulin resistance and systemic metabolic disturbances, adipogenesis, the formation of new adipocytes and healthy adipose tissue expansion are associated with metabolic benefits. Understanding the molecular mechanisms governing adipogenesis is of great clinical potential to efficiently restore metabolic health in obesity. Here we investigate the role of heart and neural crest derivatives-expressed 2 (HAND2) in adipogenesis.!##!Methods!#!Human white adipose tissue (WAT) was collected from two cross-sectional studies of 318 and 96 individuals. In vitro, for mechanistic experiments we used primary adipocytes from humans and mice as well as human multipotent adipose-derived stem (hMADS) cells. Gene silencing was performed using siRNA or genetic inactivation in primary adipocytes from loxP and or tamoxifen-inducible Cre-ERT2 mouse models with Cre-encoding mRNA or tamoxifen, respectively. Adipogenesis and adipocyte metabolism were measured by Oil Red O staining, quantitative PCR (qPCR), microarray, glucose uptake assay, western blot and lipolysis assay. A combinatorial RNA sequencing (RNAseq) and ChIP qPCR approach was used to identify target genes regulated by HAND2. In vivo, we created a conditional adipocyte Hand2 deletion mouse model using Cre under control of the Adipoq promoter (Hand2!##!Results!#!We found that HAND2 is an obesity-linked white adipocyte transcription factor regulated by glucocorticoids that was necessary but insufficient for adipocyte differentiation in vitro. In a large cohort of humans, WAT HAND2 expression was correlated to BMI. The HAND2 gene was enriched in white adipocytes compared with brown, induced early in differentiation and responded to dexamethasone (DEX), a typical glucocorticoid receptor (GR, encoded by NR3C1) agonist. Silencing of NR3C1 in hMADS cells or deletion of GR in a transgenic conditional mouse model results in diminished HAND2 expression, establishing that adipocyte HAND2 is regulated by glucocorticoids via GR in vitro and in vivo. Furthermore, we identified gene clusters indirectly regulated by the GR-HAND2 pathway. Interestingly, silencing of HAND2 impaired adipocyte differentiation in hMADS and primary mouse adipocytes. However, a conditional adipocyte Hand2 deletion mouse model using Cre under control of the Adipoq promoter did not mirror these effects on adipose tissue differentiation, indicating that HAND2 was required at stages prior to Adipoq expression.!##!Conclusions/interpretation!#!In summary, our study identifies HAND2 as a novel obesity-linked adipocyte transcription factor, highlighting new mechanisms of GR-dependent adipogenesis in humans and mice.!##!Data availability!#!Array data have been submitted to the GEO database at NCBI (GSE148699).
1000 Sacherschließung
lokal Mice, Inbred C57BL [MeSH]
lokal Aged [MeSH]
lokal hMADS
lokal Transcription Factors/genetics [MeSH]
lokal Glucocorticoid receptor
lokal Male [MeSH]
lokal Dexamethasone
lokal HAND2
lokal Obesity/genetics [MeSH]
lokal Human adipose tissue
lokal Differentiation
lokal Obesity
lokal Female [MeSH]
lokal Adult [MeSH]
lokal Transcription factor
lokal Humans [MeSH]
lokal Adipocytes
lokal Adipose Tissue, Brown/metabolism [MeSH]
lokal Middle Aged [MeSH]
lokal Cross-Sectional Studies [MeSH]
lokal Animals [MeSH]
lokal Gene Silencing [MeSH]
lokal Mice, Knockout [MeSH]
lokal Mice [MeSH]
lokal Article
lokal Glucocorticoids/pharmacology [MeSH]
lokal Basic Helix-Loop-Helix Transcription Factors/genetics [MeSH]
lokal Young Adult [MeSH]
lokal Signal Transduction [MeSH]
lokal Adipocytes/metabolism [MeSH]
lokal Gene Expression Regulation/physiology [MeSH]
lokal Adipogenesis/physiology [MeSH]
lokal Mesenchymal stem cells
lokal Real-Time Polymerase Chain Reaction [MeSH]
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0001-6320-5546|https://frl.publisso.de/adhoc/uri/VHNva2Fub3MsIEZvaXZvcy1GaWxpcHBvcw==|https://orcid.org/0000-0002-1576-8499|https://frl.publisso.de/adhoc/uri/S290c2NoaSwgU3RlZmFu|https://orcid.org/0000-0001-7193-5645|https://orcid.org/0000-0002-7176-4724|https://frl.publisso.de/adhoc/uri/Vm9nbCwgRWxlbmEgUy4=|https://orcid.org/0000-0003-3169-479X|https://orcid.org/0000-0003-2998-3613|https://orcid.org/0000-0002-2112-4243|https://frl.publisso.de/adhoc/uri/SGFzcywgRGFuaWVsYQ==|https://orcid.org/0000-0001-7796-4957|https://orcid.org/0000-0002-6053-7606|https://frl.publisso.de/adhoc/uri/TWF0dGlqc3NlbiwgRnJpdHM=|https://frl.publisso.de/adhoc/uri/TWFpZGEsIEFkcmlhbm8=|https://orcid.org/0000-0003-3300-3446|https://orcid.org/0000-0003-3402-9840|https://orcid.org/0000-0003-4324-2547|https://frl.publisso.de/adhoc/uri/VmlydGFuZW4sIEtpcnNpIEEu|https://frl.publisso.de/adhoc/uri/QmVja2VycywgSm9oYW5uZXM=|https://orcid.org/0000-0001-6795-8430|https://orcid.org/0000-0002-4220-4779|https://orcid.org/0000-0003-0208-2065|https://orcid.org/0000-0003-3691-275X|https://orcid.org/0000-0003-4650-7387|https://orcid.org/0000-0001-7840-3991|https://orcid.org/0000-0003-3950-3652
1000 Hinweis
  • DeepGreen-ID: f37dca14dcbd4c6fb8b213687fe95158 ; metadata provieded by: DeepGreen (https://www.oa-deepgreen.de/api/v1/), LIVIVO search scope life sciences (http://z3950.zbmed.de:6210/livivo), Crossref Unified Resource API (https://api.crossref.org/swagger-ui/index.html), to.science.api (https://frl.publisso.de/), ZDB JSON-API (beta) (https://zeitschriftendatenbank.de/api/), lobid - Dateninfrastruktur für Bibliotheken (https://lobid.org/resources/search)
1000 Label
1000 Dateien
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6451902.rdf
1000 Erstellt am 2023-05-12T10:40:19.282+0200
1000 Erstellt von 322
1000 beschreibt frl:6451902
1000 Zuletzt bearbeitet 2023-10-24T07:33:04.431+0200
1000 Objekt bearb. Tue Oct 24 07:33:04 CEST 2023
1000 Vgl. frl:6451902
1000 Oai Id
  1. oai:frl.publisso.de:frl:6451902 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

View source