An international team of scientists from the Korea Advanced Institute of Science and Technology (KAIST) has identified a key epigenetic mechanism capable of blocking the transformation of cells into fat cells. The discovery could eventually lead to new approaches in the treatment of obesity and type 2 diabetes. The study was published in the journal Science Advances.

At the center of the research is the protein PPARγ — the so-called “master regulator” of fat cell (adipocyte) formation. When active, it triggers an entire network of genes that lock the cell into a fat-specific identity. For this reason, PPARγ has long been considered a major target in metabolic disease research.

However, the scientists showed that the action of this protein can be suppressed not by altering DNA itself, but through an epigenetic mechanism — a fine-tuning of gene activity. Two proteins, YAP and TAZ, which are part of the Hippo signaling pathway that controls organ growth and cellular “decisions” such as division, death, or differentiation, play a key role in this process.

As it turned out, YAP and TAZ trigger a chain of chemical reactions that switch off the genes activated by PPARγ. Even when a cell receives a signal to become a fat cell, YAP and TAZ can override it and keep the cell in a less specialized state.

Experiments on cells and mice showed that when the Hippo signaling pathway — which normally restrains YAP and TAZ activity — is disrupted, fat cells partially lose their characteristics. They do not fully revert to stem cells, but they lose typical adipocyte features and begin to behave like precursor cells.

“This is the first study to show that fat cell differentiation is strictly controlled at the epigenetic level, not only through classical gene regulation,” said lead author, molecular biologist Dae-Sik Lim.

The authors emphasize that an excess of fat cells or their accumulation in the “wrong” locations is directly linked to the development of cardiovascular and metabolic diseases. At the same time, already formed fat cells are extremely difficult to eliminate: during weight loss, they usually only shrink in size rather than disappear.

The new findings offer a fresh perspective on fat tissue formation and could eventually lead to more precise and personalized strategies for treating obesity. However, the research has so far been conducted only in mice, and many years of work will be needed before clinical applications in humans become possible.

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