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14-3-3ζ coordinates adipogenesis of visceral fat

Lim, Gareth E., Albrecht, Tobias, Piske, Micah, Sarai, Karnjit, Lee, Jason T.C., Ramshaw, Hayley S., Sinha, Sunita, Guthridge, Mark A., Acker-Palmer, Amparo, Lopez, Angel F., Clee, Susanne M., Nislow, Corey and Johnson, James D. 2015, 14-3-3ζ coordinates adipogenesis of visceral fat, Nature communications, vol. 6, no. 1, doi: 10.1038/ncomms8671.

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Title 14-3-3ζ coordinates adipogenesis of visceral fat
Author(s) Lim, Gareth E.
Albrecht, Tobias
Piske, Micah
Sarai, Karnjit
Lee, Jason T.C.
Ramshaw, Hayley S.
Sinha, Sunita
Guthridge, Mark A.ORCID iD for Guthridge, Mark A. orcid.org/0000-0002-0536-3471
Acker-Palmer, Amparo
Lopez, Angel F.
Clee, Susanne M.
Nislow, Corey
Johnson, James D.
Journal name Nature communications
Volume number 6
Issue number 1
Article ID 7671
Total pages 16
Publisher Nature Publishing Group
Place of publication London, Eng.
Publication date 2015
ISSN 2041-1723
2041-1723
Summary The 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/p27Kip1. Indeed, concomitant knockdown of p27Kip1 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 p27Kip1 abundance. Together, our in vivo and in vitro findings demonstrate that 14-3-3ζ is a critical upstream driver of adipogenesis.
Language eng
DOI 10.1038/ncomms8671
Indigenous content off
Field of Research MD Multidisciplinary
HERDC Research category C1 Refereed article in a scholarly journal
Free to Read? Yes
Persistent URL http://hdl.handle.net/10536/DRO/DU:30132250

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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.