In a major breakthrough, scientists have identified a rather elusive protein involved in the production of ‘good’ fat, brown fat, and found it can even boost the formation of these cells in white fat. Understanding how to ‘switch on’ the creation of this type of energy-burning cell opens the door to novel weight-loss treatments that have eluded researchers to date.
Brown adipose tissue (BAT) is essential for producing heat from blood sugar and fat molecules, through a process called thermogenesis. It also requires a lot of energy (or calories) to fuel this. Unfortunately, by the time we reach adulthood, most of our brown fat cells have given way to white adipose tissue (WAT), which has a less efficient energy-burning system, and tends to act more as storage space for the excess calories we eat.
Elite athletes can have as little as 3% WAT throughout their body, while adults with obesity can have as much as 70% – and as such, it becomes increasingly difficult to lose weight.
But researchers at the University Hospital Bonn in Germany believe they have cracked the code that could help adults swing the pendulum back to packing more good fat, and creating ‘beige fat’, or turning the white stuff brown.
"Exercise and dieting are not enough to effectively and permanently shed the pounds," says corresponding author Alexander Pfeifer, professor and Director of the Institute of Pharmacology and Toxicology at the University Hospital Bonn. "Our energy-dense foods lead to energy being stored in white fat. But losing weight isn’t that easy, as the body saves energy in response to a low-calorie diet. So our goal is to achieve additional energy release."
Along with researchers from the University Medical Center Hamburg-Eppendorf, Helmholtz Munich and the University of Toulouse-Paul Sabatier, the Bonn team looked at the cAMP signaling pathway in fat metabolism.
“We therefore asked how brown fat mass can be increased while simultaneously reducing bad white fat," said Bonn postdoctoral researcher Laia Reverte-Salisa, also first author of the study.
In a mouse model, the team discovered that a fairly unknown protein called EPAC1 – or exchange proteins directly activated by cAMP – was key to the growth of brown fat cells. This pathway and protein are also found in human fat cells, and using an organoid model to represent human brown fat, the researchers confirmed that EPAC1’s function was the same.
"Our study shows that EPAC1 is an attractive target to increase brown fat mass and thus also energy expenditure," said Pfeifer.
What’s more, they found that an EPAC1 gene variant interrupted the protein’s function and was linked to increased body mass index (BMI). The scientists believe that by harnessing the brown-fat-cell-stimulating power of EPAC1, there’s a clear path forward in the development of novel therapeutics that make losing weight and keeping it off much easier.
The research was published in the journal Nature Cell Biology.
Source: University Hospital Bonn
