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14-3-3ζ coordinates adipogenesis of visceral fat

Author

Listed:
  • Gareth E. Lim

    (University of British Columbia)

  • Tobias Albrecht

    (University of British Columbia)

  • Micah Piske

    (University of British Columbia)

  • Karnjit Sarai

    (University of British Columbia)

  • Jason T. C Lee

    (University of British Columbia)

  • Hayley S. Ramshaw

    (The Centre for Cancer Biology, SAPathology and University of South Australia)

  • Sunita Sinha

    (University of British Columbia)

  • Mark A. Guthridge

    (Australian Centre for Blood Diseases, Monash University)

  • Amparo Acker-Palmer

    (Institute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences, University of Frankfurt)

  • Angel F. Lopez

    (The Centre for Cancer Biology, SAPathology and University of South Australia)

  • Susanne M. Clee

    (University of British Columbia)

  • Corey Nislow

    (University of British Columbia)

  • James D. Johnson

    (University of British Columbia)

Abstract

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.

Suggested Citation

  • Gareth 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 N, 2015. "14-3-3ζ coordinates adipogenesis of visceral fat," Nature Communications, Nature, vol. 6(1), pages 1-17, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8671
    DOI: 10.1038/ncomms8671
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    Cited by:

    1. Brahim Aissani & Howard W Wiener & Kui Zhang, 2016. "Fine Mapping of the Body Fat QTL on Human Chromosome 1q43," PLOS ONE, Public Library of Science, vol. 11(4), pages 1-13, April.

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