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BMP4 and BMP7 induce the white-to-brown transition of primary human adipose stem cells

Authors: M. Elsen; S. Raschke; N. Tennagels; U. Schwahn; T. Jelenik; M. Roden; T. Romacho; +1 Authors

BMP4 and BMP7 induce the white-to-brown transition of primary human adipose stem cells

Abstract

While white adipose tissue (AT) is an energy storage depot, brown AT is specialized in energy dissipation. Uncoupling protein 1 (UCP1)-expressing adipocytes with a different origin than classical brown adipocytes have been found in white AT. These “brite” (brown-in-white) adipocytes may represent a therapeutic target to counteract obesity. Bone morphogenetic proteins (BMPs) play a role in the regulation of adipogenesis. Based on studies with murine cells, BMP4 is assumed to induce stem cell commitment to the white adipocyte lineage, whereas BMP7 promotes brown adipogenesis. There is evidence for discrepancies between mouse and human AT. Therefore, we compared the effect of BMP4 and BMP7 on white-to-brown transition in primary human adipose stem cells (hASCs) from subcutaneous AT. Long-term exposure of hASCs to recombinant BMP4 or BMP7 during differentiation increased adipogenesis, as determined by lipid accumulation and peroxisome proliferator-activated receptor-γ (PPARγ) expression. Not only BMP7, but also BMP4, increased UCP1 expression in hASCs and decreased expression of the white-specific marker TCF21. The ability of hASCs to induce UCP1 in response to BMP4 and BMP7 markedly differed between donors and could be related to the expression of the brite marker CD137. However, mitochondrial content and oxygen consumption were not increased in hASCs challenged with BMP4 and BMP7. In conclusion, we showed for the first time that BMP4 has similar effects on white-to-brown transition as BMP7 in our human cell model. Thus the roles of BMP4 and BMP7 in adipogenesis cannot always be extrapolated from murine to human cell models.

Keywords

Adult, Adipogenesis, Adipose Tissue, White, Bone Morphogenetic Protein 7, Adipocytes, White, Primary Cell Culture, Bone Morphogenetic Protein 4, Lipid Metabolism, Ion Channels, Mitochondria, Mitochondrial Proteins, PPAR gamma, Adipocytes, Brown, Oxygen Consumption, Adipose Tissue, Brown, Gene Expression Regulation, Cell Transdifferentiation, Humans, Female, Cells, Cultured

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
144
Top 1%
Top 10%
Top 1%