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

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30 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

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