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

doi:10.1016/j.celrep.2023.112088

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

5 Citations (Scopus)

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 Zfp423^GFP 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 language	English
Article number	112088
Journal	Cell Reports
Volume	42
Issue number	2
Pages (from-to)	112088
ISSN	2211-1247
DOIs	https://doi.org/10.1016/j.celrep.2023.112088
Publication status	Published - 28.02.2023

Funding

This work was funded by grants from the Deutsche Forschungsgemeinschaft to K.K. ( DFG; KR 4258/3-1 and SFB1052/B12 ). We thank the core unit “Fluoreszenz-Technologien” for flow cytometry analysis. Schematic figures were created with BioRender.com (agreement number EY24PUMIOE, MD24PUMIPX, GT24PUMIRD, PB24QA2V56, FY24VQ1A4K).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Areas and Centers

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

DFG Research Classification Scheme

2.22-17 Endocrinology, Diabetology, Metabolism

Access to Document

10.1016/j.celrep.2023.112088

Cite this

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. (2023). Thyroid hormones regulate Zfp423 expression in regionally distinct adipose depots through direct and cell-autonomous action. Cell Reports, 42(2), 112088. Article 112088. https://doi.org/10.1016/j.celrep.2023.112088

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

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.",

author = "Lisa Roth and Kornelia Johann and H{\"o}nes, \{Georg Sebastian\} and Rebecca Oelkrug and Leonie Wagner and Anne Hoffmann and Knut Krohn and Moeller, \{Lars C.\} and Juliane Weiner and Heiker, \{John T.\} and Nora Kl{\"o}ting and Anke T{\"o}njes and Michael Stumvoll and Matthias Bl{\"u}her and Jens Mittag and Kerstin Krause",

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year = "2023",

month = feb,

day = "28",

doi = "10.1016/j.celrep.2023.112088",

language = "English",

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Roth, L, Johann, K, Hönes, GS, Oelkrug, R, Wagner, L, Hoffmann, A, Krohn, K, Moeller, LC, Weiner, J, Heiker, JT, Klöting, N, Tönjes, A, Stumvoll, M, Blüher, M, Mittag, J & Krause, K 2023, 'Thyroid hormones regulate Zfp423 expression in regionally distinct adipose depots through direct and cell-autonomous action', Cell Reports, vol. 42, no. 2, 112088, pp. 112088. https://doi.org/10.1016/j.celrep.2023.112088

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T1 - Thyroid hormones regulate Zfp423 expression in regionally distinct adipose depots through direct and cell-autonomous action

AU - Roth, Lisa

AU - Johann, Kornelia

AU - Hönes, Georg Sebastian

AU - Oelkrug, Rebecca

AU - Wagner, Leonie

AU - Hoffmann, Anne

AU - Krohn, Knut

AU - Moeller, Lars C.

AU - Weiner, Juliane

AU - Heiker, John T.

AU - Klöting, Nora

AU - Tönjes, Anke

AU - Stumvoll, Michael

AU - Blüher, Matthias

AU - Mittag, Jens

AU - Krause, Kerstin

PY - 2023/2/28

Y1 - 2023/2/28

N2 - 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.

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

Abstract

Funding

UN SDGs

Research Areas and Centers

DFG Research Classification Scheme

Access to Document

Other files and links

Fingerprint

CRC/TRR 296 LocoTact: Local control of TH action

Cite this

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

Abstract

Funding

UN SDGs

Research Areas and Centers

DFG Research Classification Scheme

Access to Document

Other files and links

Fingerprint

Projects

CRC/TRR 296 LocoTact: Local control of TH action

Cite this