Mammals are known to have three types of fat tissues: white, beige, and brown fat. While white adipose tissues (WAT) mainly function to store energy, beige and brown adipose tissues (BAT) consume fat and sugars to generate heat. Beige fat develops in the WAT depots in response to stimuli like cold exposure and adrenergic agonists, a process known as “WAT browning”. Lineage-tracing experiments by other groups showed that brown adipocytes and muscle progenitor cells (MPC) derive from the same embryonic progenitor cells that express Pax7 and Myf5. Our recent work revealed a molecular switch that controls the cell fate choice in the Pax7+ progenitor cells. E2F4 was found to act as a transcription repressor to repress the expression of Prdm16, the lineage-determination gene for BAT....[ Read more ]

Mammals are known to have three types of fat tissues: white, beige, and brown fat. While white adipose tissues (WAT) mainly function to store energy, beige and brown adipose tissues (BAT) consume fat and sugars to generate heat. Beige fat develops in the WAT depots in response to stimuli like cold exposure and adrenergic agonists, a process known as “WAT browning”. Lineage-tracing experiments by other groups showed that brown adipocytes and muscle progenitor cells (MPC) derive from the same embryonic progenitor cells that express Pax7 and Myf5. Our recent work revealed a molecular switch that controls the cell fate choice in the Pax7+ progenitor cells. E2F4 was found to act as a transcription repressor to repress the expression of Prdm16, the lineage-determination gene for BAT. As Prdm16 is also upregulated in beige adipocytes during WAT browning, we hypothesized that E2F4 is also a key regulator during WAT browning. In my current study, I found that there were some mature adipocytes and progenitor cells in the WAT depots that derived from the Myf5- expressing progenitors. Knocking down E2F4 in both Myf5⁺ or Myf5^- white fat progenitor cells upregulated Prdm16 and generated more UCP1+ beige adipocytes. This supported our hypothesis that E2F4 plays an important role in the development of beige fat. We are now in the process of generating an adipocyte-specific E2F4 knockout mouse line to further examine the role of E2F4 in WAT browning in vivo.