14-3-3{zeta} coordinates adipogenesis of visceral fat

Gareth Lim, Tobias Albrecht, Micah Piske, Karnjit Sarai, Jason T C Lee, Hayley S Ramshaw, Sunita Sinha, Mark Andrew Guthridge, Amparo Acker-Palmer, Angel F Lopez, Susanne M Clee, Corey Nislow, James D Johnson

Research output: Contribution to journalArticleResearchpeer-review

25 Citations (Scopus)

Abstract

The proteins that coordinate complex adipogenic transcriptional networks are poorly understood. 14-3-3? is a molecular adaptor protein that regulates insulin signalling and transcription factor networks. Here we report that 14-3-3? -knockout mice are strikingly lean from birth with specific reductions in visceral fat depots. Conversely, transgenic 14-3-3? overexpression potentiates obesity, without exacerbating metabolic complications. Only the 14-3-3? isoform is essential for adipogenesis based on isoform-specific RNAi. Mechanistic studies show that 14-3-3? depletion promotes autophagy-dependent degradation of C/EBP-d, preventing induction of the master adipogenic factors, Ppar? and C/EBP-a. Transcriptomic data indicate that 14-3-3? 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 14-3-3? knockdown in vitro. Adipocyte precursors in 14-3-3? KO embryos also appear to have greater Gli3 and p27Kip1 abundance. Together, our in vivo and in vitro findings demonstrate that 14-3-3? is a critical upstream driver of adipogenesis.
Original languageEnglish
Pages (from-to)1 - 17
Number of pages17
JournalNature Communications
Volume6
Issue number(Art. No: 7671)
DOIs
Publication statusPublished - 2015

Cite this

Lim, G., Albrecht, T., Piske, M., Sarai, K., Lee, J. T. C., Ramshaw, H. S., ... Johnson, J. D. (2015). 14-3-3{zeta} coordinates adipogenesis of visceral fat. Nature Communications, 6((Art. No: 7671)), 1 - 17. https://doi.org/10.1038/ncomms8671
Lim, Gareth ; Albrecht, Tobias ; Piske, Micah ; Sarai, Karnjit ; Lee, Jason T C ; Ramshaw, Hayley S ; Sinha, Sunita ; Guthridge, Mark Andrew ; Acker-Palmer, Amparo ; Lopez, Angel F ; Clee, Susanne M ; Nislow, Corey ; Johnson, James D. / 14-3-3{zeta} coordinates adipogenesis of visceral fat. In: Nature Communications. 2015 ; Vol. 6, No. (Art. No: 7671). pp. 1 - 17.
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Lim, G, Albrecht, T, Piske, M, Sarai, K, Lee, JTC, Ramshaw, HS, Sinha, S, Guthridge, MA, Acker-Palmer, A, Lopez, AF, Clee, SM, Nislow, C & Johnson, JD 2015, '14-3-3{zeta} coordinates adipogenesis of visceral fat', Nature Communications, vol. 6, no. (Art. No: 7671), pp. 1 - 17. https://doi.org/10.1038/ncomms8671

14-3-3{zeta} coordinates adipogenesis of visceral fat. / Lim, Gareth; Albrecht, Tobias; Piske, Micah; Sarai, Karnjit; Lee, Jason T C; Ramshaw, Hayley S; Sinha, Sunita; Guthridge, Mark Andrew; Acker-Palmer, Amparo; Lopez, Angel F; Clee, Susanne M; Nislow, Corey; Johnson, James D.

In: Nature Communications, Vol. 6, No. (Art. No: 7671), 2015, p. 1 - 17.

Research output: Contribution to journalArticleResearchpeer-review

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Lim G, Albrecht T, Piske M, Sarai K, Lee JTC, Ramshaw HS et al. 14-3-3{zeta} coordinates adipogenesis of visceral fat. Nature Communications. 2015;6((Art. No: 7671)):1 - 17. https://doi.org/10.1038/ncomms8671