Biology Department, American University, Washington DC, 20016, USA.
Cells. 2020 May 7;9(5):1148. doi: 10.3390/cells9051148.
Expansion of subcutaneous adipose tissue by differentiation of new adipocytes has been linked to improvements in metabolic health. However, an expandability limit has been observed wherein new adipocytes cannot be produced, the existing adipocytes become enlarged (hypertrophic) and lipids spill over into ectopic sites. Inappropriate ectopic storage of these surplus lipids in liver, muscle, and visceral depots has been linked with metabolic dysfunction. Here we show that Neuregulin-1 (NRG1) serves as a regulator of adipogenic differentiation in subcutaneous primary human stem cells. We further demonstrate that DNA methylation modulates NRG1 expression in these cells, and a 3-day exposure of stem cells to a recombinant NRG1 peptide fragment is sufficient to reprogram adipogenic cellular differentiation to higher levels. These results define a novel molecular adipogenic rheostat with potential implications for the expansion of adipose tissue in vivo.
脂肪组织的扩张是通过新脂肪细胞的分化来实现的，这与改善代谢健康有关。然而，已经观察到存在一个可扩展性极限，此时无法产生新的脂肪细胞，现有的脂肪细胞会变大（肥大），脂质溢出到异位部位。这些多余的脂质在肝脏、肌肉和内脏脂肪组织中的异位储存不当与代谢功能障碍有关。在这里，我们发现神经调节蛋白 1（NRG1）是调节皮下原代人干细胞成脂分化的调节剂。我们进一步证明，DNA 甲基化调节这些细胞中 NRG1 的表达，并且将干细胞暴露于重组 NRG1 肽片段 3 天足以将成脂细胞分化重新编程到更高水平。这些结果定义了一个新的分子脂肪形成变阻器，可能对体内脂肪组织的扩张具有重要意义。
