Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 1 - 17 |
| Number of pages | 17 |
| Journal | Nature Communications |
| Volume | 6 |
| Issue number | (Art. No: 7671) |
| DOIs | |
| Publication status | Published - 2015 |
Cite this
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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 journal › Article › Research › peer-review
TY - JOUR
T1 - 14-3-3{zeta} coordinates adipogenesis of visceral fat
AU - Lim, Gareth
AU - Albrecht, Tobias
AU - Piske, Micah
AU - Sarai, Karnjit
AU - Lee, Jason T C
AU - Ramshaw, Hayley S
AU - Sinha, Sunita
AU - Guthridge, Mark Andrew
AU - Acker-Palmer, Amparo
AU - Lopez, Angel F
AU - Clee, Susanne M
AU - Nislow, Corey
AU - Johnson, James D
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
UR - http://www.nature.com.ezproxy.lib.monash.edu.au/ncomms/2015/150729/ncomms8671/full/ncomms8671.html
U2 - 10.1038/ncomms8671
DO - 10.1038/ncomms8671
M3 - Article
VL - 6
SP - 1
EP - 17
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - (Art. No: 7671)
ER -