Bone Morphogenetic Proteins 4 and 7 Increase Human White and Brown Adipocyte Thermogenic Capacity

Adipocytes exist along a functional spectrum: white adipocytes are energy storing while brown adipocytes have thermogenic capacity such that activation may counteract obesity-related disease. In between are UCP1-expressing beige adipocytes, which can transition between these two energetic states. We previously showed that bone morphogenetic protein 7 (BMP7), a member of the transforming growth factor-β (TGFβ) superfamily, enables differentiation of brown preadipocytes to mature thermogenic cells. To see if immortalized, clonal human white and brown preadipocytes (hWA and hBA, respectively) would become more thermogenic in response to BMP exposure, we treated them with BMP7 or BMP4 for the first 7d of a 30d differentiation protocol. In hBA, absence of either BMP7 or BMP4 led to lower expression of brown-specific markers and oxygen consumption relative to 7d with either BMP. hWA treated for 7d with either BMP did not increase expression of thermogenic protein UCP1 nor induce a brown-like transcription profile. However, BMP-treated hWA produced adipocytes that had higher basal and drug-induced maximal oxygen consumption, which was UCP1-independent and due substantially to the futile creatine cycle (FCC). Our results demonstrate that energetically quiescent human white preadipocytes can be pushed into an energy expending phenotype without transdifferentiation into beige adipocytes, providing a new approach to treat obesity-related metabolic disease.