Researchers have found that a protein often located on the surface of fat droplets within cells — and especially abundant in the muscles of endurance athletes — can kick-off the more efficient and healthful breakdown of fat. The findings could have significant implications for development of new ways to treat obesity and Type-2 diabetes, said senior author of the study Perry Bickel, Associate Professor of Internal Medicine at the University of Texas Southwestern Medical Centre in the US.
The study, published online in the journal Nature Communications, reports a new role for the protein, Perilipin 5, in the cell nucleus as a regulator of fat metabolism. 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, Bickel said. Trying to break down large amounts of fat can overload the body’s metabolic system, swamping the tiny cellular mitochondria whose job is to turn fat into fuel for work or heat, he explained.
“If you overload the factory with fuel, then it does not work well,” Bickel added. 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, and the new 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.
In experiments with cultured cells and mice, the research team 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 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,” Bickel said.