Bone morphogenetic protein 2 is a depot-specific regulator of human adipogenesis
Open accessAbstract
BACKGROUND: Bone morphogenetic proteins (BMPs) regulate adipogenesis but it is not clear whether they influence regional adipose tissue (AT) development in humans. OBJECTIVE: To characterise BMP2 expression, BMP2-SMAD1/5/8 signalling, and BMP2's potential effect on proliferation and adipogenesis in human subcutaneous abdominal and gluteal AT and its constituent preadipocytes. METHODS: BMP2 expression was measured in whole AT and immortalised preadipocytes via qPCR and Western blot; secreted/circulating BMP2 was measured by ELISA. The effect of BMP2 on preadipocyte proliferation was evaluated using a fluorescent assay. BMP2's effect on adipogenesis in immortalised preadipocytes was determined via qPCR of adipogenic markers and cellular triacylglycerol (TAG) accumulation. BMP2-SMAD1/5/8 signalling was assessed in immortalised preadipocytes via Western blot and qPCR of ID1 expression. RESULTS: BMP2 was expressed and released by abdominal and gluteal AT and preadipocytes. Exogenous BMP2 dose dependently promoted adipogenesis in abdominal preadipocytes only; 50 ng/ml BMP2 increased PPARG2 expression (10-fold compared to vehicle, p < 0.001) and TAG accumulation (3-fold compared to vehicle; p < 0.001). BMP2 stimulated SMAD1/5/8 phosphorylation and ID1 expression in abdominal and gluteal preadipocytes but this was blocked by 500 nM K02288, a type 1 BMP receptor inhibitor (p < 0.001). Co-administration of 500 nM K02288 also inhibited the pro-adipogenic effect of 50 ng/ml BMP2 in abdominal cells; >90% inhibition of TAG accumulation (p < 0.001) and ~50% inhibition of PPARG2 expression (p < 0.001). The endogenous iron regulator erythroferrone reduced BMP2-SMAD1/5/8 signalling by ~30% specifically in subcutaneous abdominal preadipocytes (p < 0.01), suggesting it plays a role in restricting the expansion of the body's largest AT depot during energy deficiency. Additionally, a waist-hip ratio-increasing common polymorphism near BMP2 is an eQTL associated with ~15% lower BMP2 expression in abdominal and gluteal AT (p < 0.05) as well as altered adipocyte size in male abdominal AT (p < 0.05). CONCLUSIONS: These data implicate BMP2-SMAD1/5/8 signalling in depot-specific preadipocyte development and abdominal AT expansion in humans.
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BMP-2 has known roles in development, tumorigenesis, and various body tissues.
“BMP-2 has known roles in development [36], on tumorigenesis, [37] and in various body tissues [38–40].”
From Keratin Scaffold Formulation Impacts rhBMP-2 Biodistribution and Bone Regeneration in a Rat Femur Defect Model (2025) · cites this paper as [39]
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- Authors
- Denton, N. F., Eghleilib, M., Al-Sharifi, S., Todorčević, M., Neville, M. J., Loh, N., Drakesmith, A., Karpe, F., & Pinnick, K. E.
- Affiliations
- University of Oxford (GB)
- Corresponding author
- Karpe, Fredrik
- Pinnick, Katherine E.
- ORCID
- Venue
- International Journal of Obesity
- Published
- 2019-07-19
- Volume
- 43
- Issue
- 12
- Pages
- 2458-2468
- ISSN
- 0307-0565 (ISSN-L)
- 1476-5497
- PMC
- PMC6892741
- OpenAlex
- W2963138219
- Cited by
- 41
- References
- 49
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 12 · 2023: 8 · 2022: 6 · 2021: 4 · 2020: 3
- FWCI
- 2.21
- Type
- journal article
- Language
- en
- Update notices
- correction (2019-10-22)
- Open access
- hybrid
- doi.org
- Locations
- International Journal of Obesity (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute for Health and Care Research
- British Heart Foundation (RG17/1/32663)
- Department of Health and Social Care
- Medical Research Council (MC_UU_00008/10)
- NIHR Oxford Biomedical Research Centre
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- BMP-2, adipogenesis, subcutaneous adipose tissue, abdominal fat, gluteal adipose tissue, preadipocytes, PPARγ2, triglyceride accumulation, erythroferrone, iron regulation, expression quantitative trait loci, waist-to-hip ratio
- MeSH terms
- Adipose Tissue, Adult, Aged, Cells, Cultured, Female, Humans, Male, Middle Aged, Signal Transduction, Body Mass Index, Adipocytes, Cell Proliferation, Adipogenesis, Smad Proteins, Receptor-Regulated, Bone Morphogenetic Protein 2
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