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

First Author  Roth L Year  2023
Journal  Cell Rep Volume  42
Issue  2 Pages  112088
PubMed ID  36753417 Mgi Jnum  J:333455
Mgi Id  MGI:7437252 Doi  10.1016/j.celrep.2023.112088
Citation  Roth L, et al. (2023) Thyroid hormones regulate Zfp423 expression in regionally distinct adipose depots through direct and cell-autonomous action. Cell Rep 42(2):112088
abstractText  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.
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