BMP7 Drives Human Adipogenic Stem Cells into Metabolically Active Beige Adipocytes

Meshail Okla, Jung‐Heun Ha, Ryan E. Temel, Soonkyu Chung

Adult humans have a substantial amount of inducible-brown (or beige) fat, which is associated with increased energy expenditure and reduced weight gain via thermogenesis. Despite the identification of key regulators of beige adipogenesis, impacts of dietary factors on adaptive thermogenesis are largely unknown, partly due to a lack of validated human cell models. Bone morphogenetic protein 7 (BMP7) is known to promote brown adipogenesis in rodent and human progenitor cells. However, controversy still surrounds the cellular identity in BMP7-mediated transition of white to brown adipocytes. The aim of this study was to confirm BMP7-derived human adipocytes as a relevant in vitro model of human beige adipocyte by verifying the cellular lineage and metabolic activity. In this study, we hypothesized that pre-exposure of the stromal vascular (SV) fraction of primary human adipogenic precursor cells (hASC) to BMP7 would convert metabolically active brown adipocytes. Our results showed that exposure of hASC to human BMP7 was associated with significant escalation of (1) UCP1 gene expression, a signature gene of brown adipocytes, (2) beige specific marker gene expression (i.e., CD137 and TMEM26), (3) glucose and fatty acid uptake, and (4) basal and cAMP-stimulated oxygen consumption rate compared to white adipocyte control. Taken together, we demonstrated that BMP7 mediates conversion of hASC into metabolically active beige adipocytes. By confirming the cellular identity and metabolic activity, this BMP7-induced human beige adipocytes from hASC should aid in the discovery and assessment of bioactive molecules to promote adaptive thermogenesis.