This protein that appears to play an important role in obesity, metabolic disease
Scientists at Scripps Research have come up with an unexpected finding of a protein that is highly expressed in fat tissue. The study has opened the door to critical new understandings about obesity, metabolism and potentially other diseases.
The results of the study were published in the Journal Nature.
The signaling protein, known as PGRMC2, had not been extensively studied in the past. Short for “progesterone receptor membrane component 2,” it had been detected in the uterus, liver and several areas of the body.
But the lab of Enrique Saez, PhD, saw that it was most abundant in fat tissue, particularly in brown fat, which turns food into heat to maintain body temperature and became interested in its function there.
The team built on their recent discovery that PGRMC2 binds to and releases an essential molecule called heme. Recently in the spotlight for its role in providing flavour to the plant-based Impossible Burger, heme holds a much more significant role in the body.
The iron-containing molecule travels within cells to enable crucial life processes such as cellular respiration, cell proliferation, cell death, and circadian rhythms.
Using biochemical techniques and advanced assays in cells, Saez and his team found that PGRMC2 is a “chaperone” of heme, encapsulating the molecule and transporting it from the cell’s mitochondria, where heme is created, to the nucleus, where it helps carry out important functions. Without a protective chaperone, heme would react with and destroy everything in its path.
Through studies involving mice, the scientists established PGRMC2 as the first intracellular heme chaperone to be described in mammals. However, they didn’t stop there, they sought to find out what happens in the body if this protein doesn’t exist to transport heme.
And that is how they made their next big discovery: Without PGRMC2 present in their fat tissues, mice that were fed a high-fat diet became intolerant to glucose and insensitive to insulin, hallmark symptoms of diabetes and other metabolic diseases.
By contrast, obese-diabetic mice that were treated with a drug to activate the PGRMC2 function showed a substantial improvement of symptoms associated with diabetes.
Brown fat, which is normally the highest in heme content, is often considered the “good fat.” One of its key roles is to generate heat to maintain body temperature. Among mice that were unable to produce PGRMC2 in their fat tissues, temperatures dropped quickly when placed in a cold environment.
“Even though their brain was sending the right signals to turn on the heat, the mice were unable to defend their body temperature,” Galmozzi says. “Without heme, you get mitochondrial dysfunction and the cell has no means to burn energy to generate heat.”
“We’re curious to know whether this protein performs the same role in other tissues where we see defects in heme that result in disease,” Saez says.
(This story has been published from a wire agency feed without modifications to the text. Only the headline has been changed.)