ATF3 suppresses 3T3-L1 adipocyte adipogenesis by transcriptionally repressing USP53

in Journal of Molecular Endocrinology
Authors:
Yuling Xu Department of Pediatrics, Affiliated Nanjing Jiangbei Hospital of Xinglin College, Nantong University, Nanjing, Jiangsu, China

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Huimin Hu Department of Pediatrics, Affiliated Nanjing Jiangbei Hospital of Xinglin College, Nantong University, Nanjing, Jiangsu, China

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Jun Li Department of Pediatrics, Affiliated Nanjing Jiangbei Hospital of Xinglin College, Nantong University, Nanjing, Jiangsu, China

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Haoyue Li Clinical Medicine, Anhui Medical University, Hefei, Anhui, China

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Man Ye Department of Pediatrics, Affiliated Nanjing Jiangbei Hospital of Xinglin College, Nantong University, Nanjing, Jiangsu, China

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https://orcid.org/0009-0006-9474-8352

Correspondence should be addressed to M Ye: Ye_leaf2@126.com

(Y Xu and H Hu contributed equally to this work)

DOI:
https://doi.org/10.1530/JME-24-0110
Volume/Issue:
Volume 74: Issue 2
Article Type:
Research Article
Article ID:
e240110
Online Publication Date:
07 Jan 2025
Copyright:
© the author(s) 2025
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Obesity is a widespread nutritional disorder, leading to a strong predisposition toward adverse health consequences. Activating transcription factor 3 (ATF3), a stress-induced transcription factor, has been documented as a therapeutic target for obesity. The intent of this project was to characterize the detailed role of ATF3 in adipogenesis in the context of obesity and its obscure downstream mechanism. After adipogenic differentiation, RT-qPCR and western blot examined ATF3 and ubiquitin-specific peptidase 53 (USP53) mRNA levels and protein levels. Adipogenesis was identified by Oil Red O staining, triglyceride (TG) levels, and western blot analysis. JASPAR database, ChIP and luciferase reporter assays predicted and validated the transcriptional regulation of USP53 by ATF3. Western blot also examined the protein levels of Ras homolog family member A (RhoA)/Rho-associated coiled-coil kinase (ROCK) pathway-involved proteins. ATF3 mRNA and protein levels were depleted in the differentiated 3T3-L1 adipocytes, and ATF3 elevation hindered the adipogenesis of 3T3-L1 adipocytes. ATF3 suppressed the transcription of USP53 as a transcription factor and lowered USP53 expression. Eventually, USP53 upregulation partially blunted the inhibitory role of ATF3 overexpression in adipogenesis and the RhoA/ROCK pathway. Consequently, ATF3 might transcriptionally inactivate USP53 to repress adipocyte adipogenesis and downregulate the RhoA/ROCK pathway.

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Online ISSN:
1479-6813
Print ISSN:
0952-5041
Copyright:
© the author(s) 2025
Article ID:
e240110
Article Type:
Research Article
Received Date:
15 Oct 2024
Rev-recd:
21 Nov 2024
Accepted Date:
06 Dec 2024
Print Publication Date:
01 Feb 2025
Online Publication Date:
07 Jan 2025
Keywords:
adipogenesis; ATF3; USP53; RhoA/ROCK pathway; transcriptional regulation

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