14-3-3ζ coordinates adipogenesis of visceral fat

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dc.contributor.authorLim, G.
dc.contributor.authorAlbrecht, T.
dc.contributor.authorPiske, M.
dc.contributor.authorSarai, K.
dc.contributor.authorLee, J.
dc.contributor.authorRamshaw, H.
dc.contributor.authorSinha, S.
dc.contributor.authorGuthridge, M.
dc.contributor.authorAcker-Palmer, A.
dc.contributor.authorLopez, A.
dc.contributor.authorClee, S.
dc.contributor.authorNislow, C.
dc.contributor.authorJohnson, J.
dc.date.issued2015
dc.description.abstractThe proteins that coordinate complex adipogenic transcriptional networks are poorly understood. 14-3-3ζ is a molecular adaptor protein that regulates insulin signalling and transcription factor networks. Here we report that 14-3-3ζ-knockout mice are strikingly lean from birth with specific reductions in visceral fat depots. Conversely, transgenic 14-3-3ζ overexpression potentiates obesity, without exacerbating metabolic complications. Only the 14-3-3ζ isoform is essential for adipogenesis based on isoform-specific RNAi. Mechanistic studies show that 14-3-3ζ depletion promotes autophagy-dependent degradation of C/EBP-δ, preventing induction of the master adipogenic factors, Pparγ and C/EBP-α. Transcriptomic data indicate that 14-3-3ζ acts upstream of hedgehog signalling-dependent upregulation of Cdkn1b/p27(Kip1). Indeed, concomitant knockdown of p27(Kip1) or Gli3 rescues the early block in adipogenesis induced by 14-3-3ζ knockdown in vitro. Adipocyte precursors in 14-3-3ζKO embryos also appear to have greater Gli3 and p27(Kip1) abundance. Together, our in vivo and in vitro findings demonstrate that 14-3-3ζ is a critical upstream driver of adipogenesis.
dc.description.statementofresponsibilityGareth E. Lim, Tobias Albrecht, Micah Piske, Karnjit Sarai, Jason T.C Lee, Hayley S. Ramshaw, Sunita Sinha, Mark A. Guthridge, Amparo Acker-Palmer, Angel F. Lopez, Susanne M. Clee, Corey Nislow, James D. Johnson
dc.identifier.citationNature Communications, 2015; 6(1):7671-1-7671-17
dc.identifier.doi10.1038/ncomms8671
dc.identifier.issn2041-1723
dc.identifier.issn2041-1723
dc.identifier.orcidRamshaw, H. [0000-0001-9909-282X]
dc.identifier.orcidLopez, A. [0000-0001-7430-0135]
dc.identifier.urihttp://hdl.handle.net/2440/94474
dc.language.isoen
dc.publisherNature
dc.rightsThis work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
dc.source.urihttps://doi.org/10.1038/ncomms8671
dc.subjectBiological sciences
dc.subjectMedical research
dc.title14-3-3ζ coordinates adipogenesis of visceral fat
dc.title.alternative14-3-3 zeta coordinates adipogenesis of visceral fat
dc.typeJournal article
pubs.publication-statusPublished

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