Scientists have made a major breakthrough in understanding how fat cells grow in size, in response to accommodating larger droplets of fat. The findings unlock a new path in tackling obesity, by reducing the amount of fat our cells can store away.
A medical research team co-led by the University of Texas Southwestern (UT Southwestern) has identified an important piece of the puzzle as to how adipocytes absorb excess lipid (fat) droplets not burnt up through metabolism, paving the way for new obesity and diabetes targets.
“This study builds upon our long-standing interest in how fat cells maintain their cellular health upon expansion," said Philipp Scherer, Professor of Internal Medicine and Cell Biology at UT Southwestern. "We show that a tiny microprotein punches far above its weight in sculpting fat biology."
Earlier UT Southwestern research had identified a protein known as seipin that was critical for healthy lipid storage across organisms, including humans. But how seipin was facilitating this remained unknown, and despite some studies naming another protein – adipogenin – in the process, scientists didn't know how it was involved.
Using cryo-electron microscopy, the researchers found that adipogenin was more than a bystander in the process, reinforcing seipin's structural integrity to enhance its ability to form and deliver lipid droplets to cells. The result is adipocytes accommodating larger lipid droplets – and increasing the size of these fat cells.
“This study nudges us a little closer to the clinic by revealing a brand-new handle on how fat cells store lipids, which matters enormously for obesity, diabetes, lipodystrophy, and fatty liver disease,” Scherer said. “Adipogenin becomes a druggable lever on seipin’s machinery, with the promise to either dampen harmful fat buildup or boost healthy adipose storage when needed.”
When the researchers knocked out adipogenin production in mice, both fat droplets and in turn fat cells were smaller, indicating that the protein plays a key role in determining the size of the lipid package being stored in adipocytes. Mice that overproduced adipogenin had fat cells that could store significantly larger lipid droplets, in turn increasing the size of the fat cells. Adipogenin, the researchers found, was bolstering the strength of seipin to enable the production and transport of fewer but larger lipid droplets – in turn increasing the size of the fat cells housing them.
"We have confirmed that adipogenin acts as a 'molecular switch' that expands the size of lipid droplets," stated the researchers, whose study has earned them the prestigious cover story in the latest issue of Science.
These findings pave the way for an entirely new approach to improving metabolic function, tackling fat before it's had a chance to be stored away – a process that can ultimately lead to obesity and make weight loss more difficult.
The research was published in the journal Science.
Source: University of Texas Southwestern
