miR-10b-5p regulates adipocyte lineage commitment and adipogenesis via targeting of Gata6 and Tubby

Kalenderoglou, N ORCID: https://orcid.org/0000-0002-2342-1743, Dimitri, F, González, CN, Vidal-Puig, A, Hobbs, J, Younis, A ORCID: https://orcid.org/0000-0002-1127-9014, Christodoulides, C, Carobbio, S and Christian, M ORCID: https://orcid.org/0000-0002-1616-4179, 2026. miR-10b-5p regulates adipocyte lineage commitment and adipogenesis via targeting of Gata6 and Tubby. Cell Communication and Signaling. ISSN 1478-811X

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Abstract

Background: Adipogenesis is a highly organised series of events that facilitates the healthy expansion of adipose tissue, beginning during embryogenesis and continuing throughout life. White adipogenesis protects against lipotoxicity, influencing insulin resistance and obesity-related comorbidities. Brown adipogenesis enhances energy expenditure, thereby counteracting weight gain, lipotoxicity and insulin resistance. Recently, there has been a significant increase in interest regarding adipocyte differentiation, mainly focusing on the interplay between microRNAs (miRNAs) and the transcriptional cascade that governs adipogenesis and metabolic dysfunction. This study aimed to identify miRNAs regulating white and brown adipocyte differentiation and define miRNA action in a stem cell model of adipogenesis.

Methods: Small RNAseq analysis of primary mouse brown and white adipocytes (WAs) identified miR-10b-5p to be upregulated in mature brown adipocytes (BAs). We generated two model systems: (1) immortalized brown preadipocytes treated with miRNA inhibitors and (2) CRISPR/Cas9 KO of miR-10b in E14 mouse embryonic stem cells (mESCs). Both cell models were differentiated into mature adipocytes. To unravel the pathways that are affected by miR-10b-5p depletion, a transcriptomic analysis was performed at key time points.

Results: Both cell models showed that miR-10b-5p depletion severely impaired differentiation into mature adipocytes, as indicated by a lack of lipid droplet formation and reduced adipogenic gene expression. Gene expression analysis supports that miR-10b-5p directs embryonic stem (ES) cells towards the mesoderm lineage, promoting commitment to preadipocytes by downregulating Gata6 and its downstream target Bmp2. Our study further demonstrated that miR-10b-5p regulates the later stages of adipogenesis, at least in part, by downregulating Tub, a direct target of miR-10b-5p. We also confirmed that miR-10b-5p alleviated the halted differentiation phenotypes of adipocytes by suppressing the G Protein signaling pathway mediated by Tubby.

Conclusions: These results evidence that miR-10b-5p inhibition plays a dynamic role in adipocyte biology, as its inhibitory effects manifest differently during the stem cell preadipocyte proliferation state and during the maturation phase of adipocytes. Collectively, our study demonstrated that miR-10b-5p may represent a new potential therapeutic target for lipodystrophy and obesity.

Item Type:	Journal article
Publication Title:	Cell Communication and Signaling
Creators:	Kalenderoglou, N., Dimitri, F., González, C.N., Vidal-Puig, A., Hobbs, J., Younis, A., Christodoulides, C., Carobbio, S. and Christian, M.
Publisher:	Springer Science and Business Media LLC
Date:	28 March 2026
ISSN:	1478-811X
Identifiers:	Number Type 10.1186/s12964-026-02834-y DOI 2601207 Other
Rights:	© The Author(s) 2026. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Divisions:	Schools > School of Science and Technology
Record created by:	Jeremy Silvester
Date Added:	08 Apr 2026 08:53
Last Modified:	08 Apr 2026 09:39
URI:	https://irep.ntu.ac.uk/id/eprint/55505

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