Korean researchers have identified a molecular switch that prevents fat cells from forming, a discovery that could open new paths for treating obesity and other metabolic diseases.

The switch involves YAP and TAZ, regulatory proteins in the Hippo signaling pathway that controls cell growth and differentiation. When activated, YAP and TAZ suppress the process by which precursor cells become fat cells, a team led by professors Lim Dae-sik and Kang Ju-young of the Department of Biological Sciences at the Korea Advanced Institute of Science and Technology (KAIST) said on Sunday.


Fat tissue forms when precursor cells that are already committed to a specific lineage develop into adipocytes, or fat cells. That transformation depends heavily on a factor known as peroxisome proliferator-activated receptor gamma (PPARG), which activates genes involved in fat cell development.

Through a series of experiments, the researchers found that YAP and TAZ regulate the activity of PPARG, effectively controlling when and how strongly fat cell formation occurs.

Under normal conditions, when YAP and TAZ remain inactive, PPARG binds to regulatory regions involved in fat cell development and activates fat cell genes. The researchers focused on what occurs when YAP and TAZ activate.

They found that activation of YAP and TAZ triggers a downstream factor known as VGLL3, which suppresses fat cell genes.

Earlier studies suggested that YAP and TAZ block fat cell formation by directly binding to PPARG. The new findings show that YAP and TAZ play a more fundamental role by controlling fat cell genes themselves.

Fat tissue contributes to a range of metabolic diseases, including obesity and fatty liver disease. The researchers say that understanding how YAP and TAZ function could open the door to more fundamental control of fat cells.

“If we can more precisely understand how the YAP and TAZ–VGLL3–PPARG pathway operates under disease conditions, it could contribute to the treatment of patients with metabolic disorders,” Lim said.

In the paper, the research team added that it identified links between VGLL3 and key metabolic indicators, including blood cholesterol levels, insulin resistance and body mass index.

“It could be used as a possible target for treating metabolic disorders,” the researchers wrote.

BY KIM MIN-JEONG [paik.jihwan@joongang.co.kr]