Surprising protein discovery could revert some severe obesity issues

21 Nov 2019

Healthy brown fat cells (green) require ample amounts of a molecule called heme, which enables the body to metabolise food properly. Image: Scripps Research

Within fat tissue, an unexpected protein has been found that opens the door to critical new understandings about obesity and metabolism.

A new discovery could lead to the development of new ways of tackling obesity and many other diseases, thanks to a protein that has appeared in an unexpected place.

Writing in Nature, scientists at the Scripps Research facility in California said that the protein PGRMC2 has previously been detected in the uterus, liver and several areas of the body. However, they have shown it is actually most abundant in fat tissue, especially in brown fat, which turns food into heat to maintain body temperature.

The discovery builds upon previous work that showed PGRMC2 – which stands for ‘progesterone receptor membrane component 2’ – releases a molecule called heme. Not only does this molecule provide flavour to the plant-based Impossible Burger, it is also crucial for bodily functions such as cell proliferation, cell death and circadian rhythms.

In testing, the Scripps researchers showed that the protein acts as a ‘chaperone’ to heme, encapsulating the molecule. It then escorts it from the cell’s mitochondria, where heme is created, to the nucleus, where it carries out important functions.

“Heme’s significance to many cellular processes has been known for a long time,” said researcher Enrique Saez. “But we also knew that heme is toxic to the cellular materials around it and would need some sort of shuttling pathway. Until now, there were many hypotheses, but the proteins that traffic heme had not been identified.”

Improved symptoms with diabetes

In testing with mice, the big breakthrough came after they noticed that without PGRMC2 in their bodies, mice fed a high-fat diet became intolerant to glucose and insensitive to insulin – hallmark symptoms of diabetes and other metabolic diseases.

Meanwhile, those treated with a drug to activate the protein showed a substantial improvement in symptoms associated with diabetes.

“Our findings suggest that modulating PGRMC2 activity in fat tissue may be a useful pharmacological approach for reverting some of the serious health effects of obesity,” Saez said.

Another aspect of the discovery showed that the mice unable to produce PGRMC2 saw their body temperature drop sharply in a cold environment. Even though their brains were sending the right signals, the lack of heme – found in abundance in brown fat – meant it couldn’t burn energy to generate heat.

If the heme chaperone was activated in other organs where the protein is present, Saez said, then it could help mitigate the effects of metabolic disorders such as non-alcoholic steatohepatitis, a major cause of liver transplantation.

Colm Gorey was a senior journalist with Silicon Republic