Scientists have identified a protein, abundantly found in muscles of endurance athletes, that can kick-start efficient breakdown of fat, a finding that may lead to new treatments for obesity and type 2 diabetes.
Researchers found a new role for the protein, Perilipin 5, in the cell nucleus as a regulator of fat metabolism.
“The finding that it was in the nucleus “was a complete surprise to us,” said Perry Bickel from University of Texas Southwestern Medical Centre in the US.
Perilipin 5, often located on the surface of fat droplets within cells, is especially abundant in the muscles of endurance athletes, researchers said.
“In obese people and rodents, excess fat can accumulate in tissues not specialised for fat storage, such as skeletal muscle, the heart, and liver. This buildup can lead to dysfunction of those tissues,” said Bickel.
According to him, trying to break down large amounts of fat can overload the body’s metabolic system, swamping the tiny cellular mitochondria whose jobs are to turn fat into fuel for work or heat.
“If you overload the factory with fuel, then it does not work well,” said Bickel.
The cells are then left with a brew of partially processed fats that can be toxic to the mitochondria and lead to the insulin resistance seen in type 2 diabetes, he said.
Endurance athletes – who paradoxically accumulate at least as much fat in their muscle cells as do obese, insulin-resistant people – have been found to have higher levels of Perilipin 5.
The findings may explain why such athletes are able to exploit the increased stored fat for fuelling exercise while avoiding the toxicity of increased muscle fat, researchers said.
In experiments with cultured cells and mice, researchers found that when cells are stimulated to release fat stored in fat droplets, Perilipin 5 can leave the surface of those droplets and move to the cell’s nucleus, where it works with another protein, PGC-1a, to encourage the creation of additional – and more efficient – mitochondria.
In this way, Perilipin 5, “helps match mitochondrial capacity to burn fat with the fat load in the cell,” said Bickel.
The findings eventually could lead to a new approach for treating obesity-related diabetes – perhaps a new drug that could mimic Perilipin 5 or an aspect of its function, he said.
The findings were published in the journal Nature Communications.