Thyroid hormones regulate Zfp423 expression in regionally distinct adipose depots through direct and cell-autonomous action

Lisa Roth, Kornelia Johann, Georg Sebastian Hönes, Rebecca Oelkrug, Leonie Wagner, Anne Hoffmann, Knut Krohn, Lars C. Moeller, Juliane Weiner, John T. Heiker, Nora Klöting, Anke Tönjes, Michael Stumvoll, Matthias Blüher, Jens Mittag, Kerstin Krause*

*Corresponding author for this work

Abstract

The hypothalamic pituitary thyroid axis is a major regulator of many differentiation processes, including adipose tissue. However, it remains unclear whether and how thyroid hormone (TH) signaling contributes to preadipocyte commitment and differentiation into mature adipocytes. Here, we show a cell-autonomous effect of TH on the transcriptional regulation of zinc finger protein 423 (Zfp423), an early adipogenic determination factor, in murine adipose depots. Mechanistically, binding of the unliganded TH receptor to a negative TH responsive element within the Zfp423 promoter activates transcriptional activity that is reversed upon TH binding. Zfp423 upregulation is associated with increased GFP+ preadipocyte recruitment in stromal vascular fraction isolated from white fat of hypothyroid Zfp423GFP reporter mice. RNA sequencing identified Zfp423-driven gene programs that are modulated in response to TH during adipogenic differentiation. Collectively, we identified Zfp423 as a key molecule that integrates TH signaling into the regulation of adipose tissue plasticity.

Original languageEnglish
Article number112088
JournalCell Reports
Volume42
Issue number2
Pages (from-to)112088
ISSN2211-1247
DOIs
Publication statusPublished - 28.02.2023

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)

DFG Research Classification Scheme

  • 205-17 Endocrinology, Diabetology, Metabolism

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