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

doi:10.1038/ncomms8671

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

Australian Centre for Blood Diseases

Research output: Contribution to journal › Article › Research › peer-review

55 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 language	English
Pages (from-to)	1 - 17
Number of pages	17
Journal	Nature Communications
Volume	6
Issue number	(Art. No: 7671)
DOIs	https://doi.org/10.1038/ncomms8671
Publication status	Published - 2015

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10.1038/ncomms8671

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title = "14-3-3{zeta} coordinates adipogenesis of visceral fat",

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.",

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

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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.

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IS - (Art. No: 7671)

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

Abstract

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