Dataset Information

Ups and downs: The PPARγ/p-PPARγ seesaw of follistatin-like 1 and integrin receptor signaling in adipogenesis.

ABSTRACT:

Objective

Although Follistatin-like protein 1 (FSTL1), as an "adipokine", is highly expressed in preadipocytes, the detail role of FSTL1 in adipogenesis and obesity remains not fully understood.

Methods

In vitro differentiation of both Fstl1^-/- murine embryonic fibroblasts (MEFs) and stromal vascular fraction (SVF) were measured to assess the specific role of FSTL1 in adipose differentiation. Fstl1 adipocyte-specific knockout mice were generated to evaluate its role in obesity development. Gene expression analysis and phosphorylation patterns were performed to check out the molecular mechanism of the biological function of FSTL1.

Results

FSTL1 deficiency inhibited preadipocytes differentiation in vitro and obesity development in vivo. Glycosylation at N142 site was pivotal for the biological effect of FSTL1 during adipogenesis; the conversion between PPARγ and p-PPARγ was the key factor for the function of FSTL1. Molecular mechanism studies showed that FSTL1 functions through the integrin/FAK/ERK signaling pathway.

Conclusions

Our results suggest that FSTL1 promotes adipogenesis by inhibiting the conversion of PPARγ to p-PPARγ through the integrin/FAK/ERK signaling pathway. Glycosylated modification at N142 of FSTL1 is the key site to exert its biological effect.

SUBMITTER: Fang D

PROVIDER: S-EPMC8683615 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Publications

Ups and downs: The PPARγ/p-PPARγ seesaw of follistatin-like 1 and integrin receptor signaling in adipogenesis.

Fang Dongliang D Shi Xinyi X Jia Xiaowei X Yang Chun C Wang Lulu L Du Baopu B Lu Tao T Shan Lin L Gao Yan Y

Molecular metabolism 20211120

<h4>Objective</h4>Although Follistatin-like protein 1 (FSTL1), as an "adipokine", is highly expressed in preadipocytes, the detail role of FSTL1 in adipogenesis and obesity remains not fully understood.<h4>Methods</h4>In vitro differentiation of both Fstl1<sup>-/-</sup> murine embryonic fibroblasts (MEFs) and stromal vascular fraction (SVF) were measured to assess the specific role of FSTL1 in adipose differentiation. Fstl1 adipocyte-specific knockout mice were generated to evaluate its role in ...[more]

PMID: 34813964

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Project description:Recent genome-wide analyses have uncovered a high accumulation of RNA polymerase II (Pol II) at the 5' end of genes. This elevated Pol II presence at promoters, referred to here as Poll II poising, is mainly (but not exclusively) attributed to temporal pausing of transcription during early elongation which, in turn, has been proposed to be a regulatory step for processes that need to be activated "on demand". Yet, the full genome-wide regulatory role of Pol II poising is yet to be delineated. To elucidate the role of Pol II poising in B cell activation, we compared Pol II profiles in resting and activated B cells. We found that while Pol II poised genes generally overlap functionally among different B cell states and correspond to the functional groups previously identified for other cell types, non-poised genes are B cell state specific. Focusing on the changes in transcription activity upon B cell activation, we found that the majority of such changes were from poised to non-poised state. The genes showing this type of transition were functionally enriched in translation, RNA processing and mRNA metabolic process. Interestingly, we also observed a transition from non-poised to poised state. Within this set of genes we identified several Immediate Early Genes (IEG), which were highly expressed in resting B cell and shifted from non-poised to poised state after B cell activation. Thus Pol II poising does not only mark genes for rapid expression in the future, but it is also associated with genes that are silenced after a burst of their expression. Finally, we performed comparative analysis of the presence of G4 motifs in the context of poised versus non-poised but active genes. Interestingly we observed a differential enrichment of these motifs upstream versus downstream of TSS depending on poising status. The enrichment of G4 sequence motifs upstream of TSS of non-poised active genes suggests a potential role of quadruplexes in expression regulation.

Dataset Information

Ups and downs: The PPARγ/p-PPARγ seesaw of follistatin-like 1 and integrin receptor signaling in adipogenesis.

Objective

Methods

Results

Conclusions

Publications

Ups and downs: The PPARγ/p-PPARγ seesaw of follistatin-like 1 and integrin receptor signaling in adipogenesis.

Similar Datasets

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