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
27/12/2025
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
26/12/2025
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
26/12/2025
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
25/12/2025
Holiday lights are twinkling, hot cocoa's on the stove and gamers are settling in for a well-earned break.
Whether staying in or heading on a winter getawa...
24/12/2025
What is AI good for? Posted by MTI Film on December 24, 2025
What is AI good for?
What is AI good for?
It's been three years since ChatGPT first cap...
24/12/2025
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
24/12/2025
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
24/12/2025
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
24/12/2025
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
24/12/2025
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
24/12/2025
Back to All News
The Boyfriend' Season 2 Unveils Heartwarming Trailer, Key...
24/12/2025
Back to All News
Love, Fights, and Everything in Between: Badly in Love' Returns for Season 2
Entertainment
24 December 2025
GlobalJapan
Link copied t...
24/12/2025
Scripps Research study links sleep variability with sleep apnea and hypertension How consumers' digital activity trackers could enable personalized health s...
23/12/2025
How guilas Cibae as Dominican Winter League Games Are Locally Produced for Glob...
23/12/2025
BitFire's Jim Akimchuk on Supplying Scalability and Customization in the Clo...
23/12/2025
CAMB.AI Enables European Athletics to Offer Multi-Language SupportPlan is to eventually offer translation into all languages spoken in EuropeBy Ken Kerschbaumer...
23/12/2025
Analysis: As sports media values trend negative, scarcity and quality are king By Callum McCarthy, Editor-at-Large
Monday, December 22, 2025 - 14:08
Print ...
23/12/2025
ESPN, Disney, and NBA Return to the Animated Altcast Fray With Second Edition of...
23/12/2025
End the Year on a High Note and Donate to the Sports Broadcasting Fund Today! By Ken Kerschbaumer, Editorial Director
Tuesday, December 23, 2025 - 12:25 pm
...
23/12/2025
A Zeus motor is hot fire tested at L3Harris' Camden, Arkansas, solid rocket ...
23/12/2025
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
23/12/2025
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
23/12/2025
Lightware will exhibit several major product innovations at ISE 2026, including the new USB-C BOOSTER-V1, Google Meet. integration for various Taurus UCX models...
23/12/2025
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
23/12/2025
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
23/12/2025
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
23/12/2025
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
23/12/2025
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
23/12/2025
Taking the Stage at Carnegie Hall-On a Global Scale Boston Conservatory Orchestra students reflect on their epic concert marking the 80th session of the UN Gene...
23/12/2025
Back to All News
Netflix's The Great Flood and Culinary Class Wars 2 Top Gl...
23/12/2025
Back to All News
Stranger Things By the Numbers: How the Global Phenomenon Shap...
23/12/2025
Experience the power of WO Automation for Radio's newest service, the System Effectiveness Review. Designed to help you achieve more, a System Effectiveness...
23/12/2025
Back to All News
How Steamy Can It Get? Single's Inferno' Season 5 Pre...
23/12/2025
Back to All News
33 Million Global Viewers on Netflix Watched Jake Paul vs. Ant...
23/12/2025
New technique lights up where drugs go in the body, cell by cell Scripps Research scientists developed a technique that maps drug binding in individual cells th...
22/12/2025
SVG New Sponsor Spotlight: Presidio's Neerav Shah on the Role of Its Captiva...
22/12/2025
Hitting the bullseye: Sky Sports readies itself for the biggest PDC World Darts ...
22/12/2025
Unique skillset: Bringing new directors to the world of darts at The Worlds with...
22/12/2025
Gravity Media prepares for a flight of fancy with the PDC World Darts Championsh...
22/12/2025
One hundred and eighty: Gravity Media on hitting the production bullseye at the ...
22/12/2025
The Famous Group's Jon Slusser on Fascinating Fans Through Immersive Content...
22/12/2025
ESPN's Meg Aronowitz on Continuing High-Quality Broadcasts of Collegiate Spo...
22/12/2025
ESPN Takes Data-Driven Storytelling to New Heights with MNF Playbook with Next ...
22/12/2025
Paramount Scores Largest Share Increase Among Distributors as Paramount and CBS...
22/12/2025
New multi-year deal integrates Roku's data to fuel Nielsen's measurement suite
Roku gains access to Nielsen's streaming ratings, showing The Roku C...
22/12/2025
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
22/12/2025
Berklee Wrapped 2025: Our Top News and Stories A look back at a year highlighted by faculty milestones, major film and television projects, Bob Dylan's ho...
22/12/2025
The works of Plato state that when humans have an experience, some level of change occurs in their brain, which is powered by memory - specifically long-term me...
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. 
