title: 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.
authors.affiliation: Paul-Langerhans-Group for Integrative Physiology, German Diabetes Center, Düsseldorf, Germany;
authors.forename: Manuela
authors.initials: M
authors.lastname: Elsen
authors.forename: Silja
authors.initials: S
authors.lastname: Raschke
authors.forename: Norbert
authors.initials: N
authors.lastname: Tennagels
authors.forename: Uwe
authors.initials: U
authors.lastname: Schwahn
authors.forename: Tomas
authors.initials: T
authors.lastname: Jelenik
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
authors.forename: Tania
authors.initials: T
authors.lastname: Romacho
authors.forename: Jürgen
authors.initials: J
authors.lastname: Eckel
mesh_terms: D052437:Adipocytes, Brown / Q000378:metabolism*; D052438:Adipocytes, White / Q000378:metabolism*; D050156:Adipogenesis; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000166:cytology / Q000378:metabolism*; D000328:Adult; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism*; D055419:Bone Morphogenetic Protein 7 / Q000378:metabolism*; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D010101:Oxygen Consumption; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism*; D013997:Time Factors; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000378:metabolism; D000071256:Uncoupling Protein 1
chemical_list: C525809:BMP4 protein, human; C525819:BMP7 protein, human; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D007473:Ion Channels; D024101:Mitochondrial Proteins; D047495:PPAR gamma; D012333:RNA, Messenger; D011994:Recombinant Proteins; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; C000604371:UCP1 protein, human; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1
keywords: adipogenesis; bone morphogenetic proteins; brite adipocytes; primary human preadipocytes