Distinct regulatory mechanisms governing embryonic versus adult adipocyte maturation

QA Wang, C Tao, L Jiang, M Shao, R Ye, Y Zhu… - Nature cell …, 2015 - nature.com
QA Wang, C Tao, L Jiang, M Shao, R Ye, Y Zhu, R Gordillo, A Ali, Y Lian, WL Holland…
Nature cell biology, 2015nature.com
Pathological expansion of adipose tissue contributes to the metabolic syndrome. Distinct
depots develop at various times under different physiological conditions. The transcriptional
cascade mediating adipogenesis is established in vitro, and centres around a core program
involving PPARγ and C/EBPα. We developed an inducible, adipocyte-specific knockout
system to probe the requirement of key adipogenic transcription factors at various stages of
adipogenesis in vivo. C/EBPα is essential for all white adipogenic conditions in the adult …
Abstract
Pathological expansion of adipose tissue contributes to the metabolic syndrome. Distinct depots develop at various times under different physiological conditions. The transcriptional cascade mediating adipogenesis is established in vitro, and centres around a core program involving PPARγ and C/EBPα. We developed an inducible, adipocyte-specific knockout system to probe the requirement of key adipogenic transcription factors at various stages of adipogenesis in vivo. C/EBPα is essential for all white adipogenic conditions in the adult stage, such as adipose tissue regeneration, adipogenesis in muscle and unhealthy expansion of white adipose tissue during high-fat feeding or due to leptin deficiency. Surprisingly, terminal embryonic adipogenesis is fully C/EBPα independent, but does however depend on PPARγ; cold-induced beige adipogenesis is also C/EBPα independent. Moreover, C/EBPα is not vital for adipocyte survival in the adult stage. We reveal a surprising diversity of transcriptional signals required at different stages of adipogenesis in vivo.
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