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.
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. (ANI)