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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