MiR-93 Controls Adiposity via Inhibition of Sirt7 and Tbx3
Open accessAbstract
Conquering obesity has become a major socioeconomic challenge. Here, we show that reduced expression of the miR-25-93-106b cluster, or miR-93 alone, increases fat mass and, subsequently, insulin resistance. Mechanistically, we discovered an intricate interplay between enhanced adipocyte precursor turnover and increased adipogenesis. First, miR-93 controls Tbx3, thereby limiting self-renewal in early adipocyte precursors. Second, miR-93 inhibits the metabolic target Sirt7, which we identified as a major driver of in vivo adipogenesis via induction of differentiation and maturation of early adipocyte precursors. Using mouse parabiosis, obesity in mir-25-93-106b(-/-) mice could be rescued by restoring levels of circulating miRNA and subsequent inhibition of Tbx3 and Sirt7. Downregulation of miR-93 also occurred in obese ob/ob mice, and this phenocopy of mir-25-93-106b(-/-) was partially reversible with injection of miR-93 mimics. Our data establish miR-93 as a negative regulator of adipogenesis and a potential therapeutic option for obesity and the metabolic syndrome.
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TBX3 is critically involved in pluripotency maintenance and lineage-specific exit from the pluripotency circuitry in mouse embryonic stem cells.
“Finally, TBX3 is not only critically involved in pluripotency maintenance but also in lineage-specific exit from the pluripotency circuitry in mouse embryonic stem cells [11–17].”
From TBX3 is dynamically expressed in pancreatic organogenesis and fine-tunes regeneration (2023) · cites this paper as [15]
The Discussion (page unavailable) says Tbx3 maintains pluripotency in pluripotent stem cells and promotes mesendodermal differentiation during embryogenesis. It does not specifically establish lineage-specific exit from the pluripotency circuitry in mouse embryonic stem cells; the paper's own experiments concern adipocyte precursors. (LLM, conf=0.85)
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- Authors
- Cioffi, M., Vallespinos-Serrano, M., Trabulo, S. M., Fernandez-Marcos, P. J., Firment, A. N., Vazquez, B. N., Vieira, C. R., Mulero, F., Camara, J. A., Cronin, U. P., Perez, M., Soriano, J., G. Galvez, B., Castells-Garcia, A., Haage, V., Raj, D., Megias, D., Hahn, S., Serrano, L., Moon, A., Aicher, A., & Heeschen, C.
- Affiliations
- Spanish National Cancer Research Centre (ES)
- Queen Mary University of London (GB)
- Ruhr University Bochum (DE)
- Rutgers, The State University of New Jersey (US)
- Corresponding author
- Aicher, Alexandra
- Heeschen, Christopher
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 12
- Issue
- 10
- Pages
- 1594-1605
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W1614016872
- Cited by
- 116
- References
- 31
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 12 · 2023: 7 · 2022: 8 · 2021: 14 · 2020: 15 · 2019: 7 · 2018: 16 · 2017: 17 · 2016: 12 · 2015: 1
- FWCI
- 12.03
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- European Commission (602783)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD046767)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- miR-93, obesity, adiposity, adipogenesis, adipocyte precursors, SIRT7, TBX3, insulin resistance, fat mass, parabiosis, ob/ob mice, metabolic syndrome, microRNA therapeutic target
- MeSH terms
- Cell Self Renewal, Adipose Tissue, Animals, Female, Insulin Resistance, Male, Mice, Inbred C57BL, Mice, Obese, Adipocytes, Mice, Knockout, T-Box Domain Proteins, Metabolic Syndrome, RNA Interference, MicroRNAs, Sirtuins, 3T3-L1 Cells, Adiposity, Adipogenesis, Mice, Adipose Tissue, White
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