The potential of brown adipogenesis and browning in porcine bone marrow-derived mesenchymal stem cells1.

Brown adipocyte lineage commitment and differentiation are under complex regulation. Brown adipocytes are derived from mesenchymal stem cells (MSC). Whether porcine bone marrow-derived MSC (BM-MSC) possess the potential to differentiate into brown adipocytes remains unclear. In the current study, we evaluated the ability of porcine BM-MSC to differentiate into brown adipocytes and browning of differentiated adipocytes. We found that similar to rodent models, bone morphogenetic protein 7 (BMP7) was able to trigger the commitment of BM-MSC to the brown adipocyte lineage by elevating expression of marker genes, nrf-1, tfam, zic1, and pgc-1α (P < 0.05). The expression of brown adipocyte-specific genes, prdm16, dio2, and cidea, was significantly induced (P < 0.05) in BMP7-treated porcine BM-MSC after hormonal induction of adipogenesis. The UCP2 and UCP3 protein levels in BMP7-treated porcine BM-MSC were higher than the control group after hormonal induction of adipogenesis, accompanied by increased mitochondrial DNA copy number and mitochondria-specific gene expression (P < 0.05). Furthermore, acute norepinephrine stimulation potentiated brown adipocyte-specific mRNA expression (P < 0.05) in differentiated adipocytes. Similarly, UCP2 and UCP3 protein levels were increased in differentiated adipocytes upon acute norepinephrine stimulation. In addition, mitochondrial DNA copy number and mitochondria-specific gene expression were also significantly increased (P < 0.05) in differentiated adipocytes after acute norepinephrine exposure. Taken together, these results demonstrate for the first time that porcine BM-MSC are able to commit to the brown adipocyte lineage and differentiate into brown adipocytes. Differentiated adipocytes derived from porcine BM-MSC have the developmental potential to transdifferentiate into brown-like adipocytes upon norepinephrine stimulation.