Little-known protein appears to play important role in obesity and metabolic disease The recently discovered protein is normally abundant in fat; without it, the body struggles to manage glucose and insulin.
November 20, 2019
LA JOLLA, CA With unexpected findings about a protein that's highly expressed in fat tissue, scientists at Scripps Research have opened the door to critical new understandings about obesity and metabolism. Their discovery, which appears in Nature, could lead to new approaches for addressing obesity and potentially many other diseases.
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.
An important role: heme's travel guide
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 flavor 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.
Heme's significance to many cellular processes has been known for a long time, says Saez, associate professor in the Department of Molecular Medicine. 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.
An innovative approach for obesity?
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's 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 PGRMC2 function showed a substantial improvement of symptoms associated with diabetes.
We saw the mice get better, becoming more glucose tolerant and less resistant to insulin, Saez says. 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.
The team also evaluated how the protein changes other functions of brown and white fat, says the study's lead author, Andrea Galmozzi, PhD. The first surprise finding was that the brown fat looked white, he says.
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.
Saez believes it's possible that activating the heme chaperone in other organs including the liver, where a large amount of heme is made could help mitigate the effects of other metabolic disorders such as non-alcoholic steatohepatitis (NASH), which is a major cause of liver transplantation today.
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.
Authors of the study, PGRMC2 is an intracellular haem chaperone critical for adipocyte function, include Andrea Galmozzi, Bernard P. Kok, Arthur S. Kim, J. Rafael Montenegro-Burke, Jae Y. Lee, Roberto Spreafico, Sarah Mosure, Verena Albert, Rigo Cintron-Colon, Cristina Godio, William R. Webb, Bruno Conti1, Laura A. Solt, Douglas Kojetin, Christopher G. Parker, John J. Peluso, James K. Pru, Gary Siuzdak, Benjamin F. Cravatt and Enrique Saez.
The work was supported by National Institutes of Health grants (DK099810, DK114785, DK121196, S10OD016357, OD016564). Two of the researchers, Kok and Albert, also were supported by fellowships from the American Heart Association.
Diabetes, Obesity and Metabolic Disorders Saez, Enrique
North America Stories
15/07/2026
The 2026 FIFA World Cup is a big deal for DAZN, which has distribution rights in three markets: Italy, Spain, and Japan. Each requires a different editorial app...
15/07/2026
As sports-media organizations manage rapidly growing content libraries and incre...
15/07/2026
HBS director of digital Johannes Franken talks SVG Europe through the operation built to serve FIFA World Cup 2026 rights holders remotely from Stratford, east ...
15/07/2026
IBC has unveiled the conference program for IBC2026, with this year's event ...
15/07/2026
Software-defined wideband RF platform supports 96-kHz monitoring, streamlined fr...
15/07/2026
New AI-powered module enables broadcasters and content owners to extract dialogu...
15/07/2026
Weeklong gathering at EBU headquarters will test new IPMX capabilities and expand certified product ecosystem...
15/07/2026
Force Tech has announced the appointment of Bryan Adams, CTS, as Vice President of Integration. Adams will oversee AV and broadcast integration project delivery...
15/07/2026
USA Sports has announced an exclusive English-language agreement with the Bundes...
15/07/2026
ITV Sport's FIFA World Cup 2026 coverage has been produced from one of the m...
15/07/2026
Program will provide professional camera kits, training, and technical support to participating local newsrooms...
15/07/2026
San Francisco church becomes first U.S. deployment of the 2 M/E production switcher...
15/07/2026
Former ESPN and NFL Network executive to advise startup league on media, distribution, technology, and fan engagement...
15/07/2026
The Houston-based RSN is the live-game home of the Astros and Rockets...
15/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
15/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
15/07/2026
GigaCloud, a leading Ukrainian cloud service provider, and Cubbit, the first geo-distributed cloud storage enabler, today announced a new Business Alliance Part...
15/07/2026
SMPTE, the global society for media professionals, technologists, and engineers, has announced the launch of the SMPTE 110th Anniversary Campaign, a fundraising...
15/07/2026
Studio Technologies, a leading manufacturer of high-quality audio, video, and fiber-optic solutions, unveils the new StudioComm Model 762 Stereo Level Control, ...
15/07/2026
COW Jobs: Producer, Virtual Events - Hybrid, Full Time, Salaried
Brie Clayton July 15, 2026
0 Comments
Producer, Virtual Events (Hybrid | Full-time | ...
15/07/2026
Brazilian media organization builds nationwide CDN with Broadpeak's high-performance software for low-latency streaming and new content distribution service...
15/07/2026
DHD announces a new utility designed to increase the efficiency of its audio mixing systems during initial installation and subsequent configuration.
Anyone w...
15/07/2026
BCNEXXT Brings Next-Generation Vipe to IBC2026, Breaking the 1:1 Channel-to-Server Ratio New innovations liberate broadcasters from legacy playout infrastructur...
15/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
15/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
15/07/2026
Home to leading manufacturers, robotics pioneers, infrastructure builders and gaming, of course, Japan is one of the world's centers of AI - building across...
14/07/2026
South end zone videoboard, cloud-based control system will be ready for 2026 football season...
14/07/2026
Redesigned website, enhanced mobile app unify content, ticketing, and personalized fan engagement...
14/07/2026
Agreement spans sponsorship sales, digital monetization, radio production, and new practice facility naming rights...
14/07/2026
Independent league adds 14 regional sports network affiliates, growing distribut...
14/07/2026
New strategy aims to unify competitions, content, fan engagement, and commercial...
14/07/2026
ESPN and Disney+ become exclusive home of PFL events in key international MMA market...
14/07/2026
Gill will oversee engineering, technology, and sports operations across the company's 64 local television stations...
14/07/2026
Submitted by North American Broadcasters Association (NABA)
As broadcasters con...
14/07/2026
Modernized mobile unit combines HOME Apps, mc 56 console, and IP infrastructure ...
14/07/2026
Every match of the 32-team tournament will air across ION and Scripps Sports platforms in English and Spanish...
14/07/2026
FloHockey to stream every game of the annual international tournament under four...
14/07/2026
Victory+ telecasts to be simulcast on TEGNA-owned station, expanding free local distribution...
14/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
14/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
14/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
14/07/2026
IBC2026 has unveiled a powerful Conference programme bringing together global media leaders, technology innovators, creators, sports organisations, broadcasters...
14/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
14/07/2026
Broadcast Solutions, a leading systems integrator and provider of innovative solutions for the broadcast media industry, has delivered two highly capable outsid...
14/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
14/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
14/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
14/07/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
14/07/2026
Telos Alliance Adds AudioShake Source Separation to Minnetonka Audio AudioToo...
Little-known protein appears to play important role in obesity and metabolic disease The recently discovered protein is normally abundant in fat; without it, the body struggles to manage glucose and insulin. 
