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Roth, L.* ; Johann, K.* ; Hönes, G.S.* ; Oelkrug, R.* ; Wagner, L.* ; Hoffmann, A. ; Krohn, K.* ; Moeller, L.C.* ; Weiner, J.* ; Heiker, J.T. ; Klöting, N. ; Tönjes, A.* ; Stumvoll, M. ; Blüher, M. ; Mittag, J.* ; Krause, K.*

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

Cell Rep. 42:112088 (2023)

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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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Adipocyte Precursor ; Adipogenesis ; Adipose Tissue ; Cp: Metabolism ; Cp: Molecular Biology ; Hypothyroidism ; Preadipocyte ; Thyroid Hormone Receptors ; Thyroid Hormones ; Zfp423; Tissue; White; Thermogenesis; Preadipocytes; Receptors; Mice

ISSN (print) / ISBN 2211-1247

e-ISSN 2211-1247

Journal Cell Reports

Quellenangaben Volume: 42, Issue: 2, Article Number: 112088

Publisher Cell Press

Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)

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Deutsche Forschungsgemeinschaft