
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
02/07/2025
Hege Wik and Odin appear in FOLKTALES by Heidi Ewing and Rachel Grady, an official selection of the 2025 Sundance Film Festival. Courtesy of Sundance Institut...
02/07/2025
(Stephen Lovekin/Shutterstock for Sundance Film Festival)
By Patty Consolazio
This one's for any person who's ever felt put down, left out, marginaliz...
02/07/2025
NEW YORK Paramount Global has agreed to pay $16 million to settle a lawsuit by President Donald Trump, ending a long-running legal saga that could clear the way...
02/07/2025
WASHINGTON The Federal Communications Commission has approved the transfer of licenses for five TV stations from Sinclair to Rincon Broadcasting, which announce...
02/07/2025
As the media industry faces an uncertain business climate and rapidly changing consumer habits, TV Tech's most popular stories from the first six months of ...
02/07/2025
PORTSMOUTH, N.H. New data shows that U.S. homes now own an average of two smart TVs, with Samsung and LG dominating the market but Roku and FireTV continue to g...
02/07/2025
LOS ANGELES Funds managed by Oaktree Capital Management have acquired FilmRise, an independent digital streaming content distributor, and merged it with Shout! ...
02/07/2025
WASHINGTON The Advanced Television Systems Committee named Luiz Fausto vice president of standards development, succeeding ATSC vice president Jerry Whitaker, w...
02/07/2025
Boston Conservatory and the Sphinx Organization Join Forces to Make Classical Ed...
02/07/2025
Progressive realism: Aurora on taking up the broadcast reins for World RX alongs...
02/07/2025
Great speed: New host broadcaster Aurora on getting the World RX 2025 season pro...
02/07/2025
Seat of its pants: Aurora boxes clever and looks ahead for the FIA as new host b...
02/07/2025
UEFA Women's Euro 2025: EBU, BBC Sport and Sunset Vine talk coverage plans, ...
02/07/2025
UEFA Women's Euro 2025: Women's Super League launches new content series...
02/07/2025
UEFA Women's Euro 2025: Ignite puts fans and players front and centre with t...
02/07/2025
Storytelling in the Live Game Broadcast: ESPN Director Jimmy Platt Breaks Down t...
02/07/2025
CONCACAF's Miguel Angel Garcia on the Gold Cup's Enhanced 2025 Productio...
02/07/2025
Black Forest Labs, one of the world's leading AI research labs, just changed the game for image generation.
The lab's FLUX.1 image models have earned g...
01/07/2025
L3Harris Technologies has delivered its second Bombardier Global 6500 missionize...
01/07/2025
MELBOURNE, Fla., July 1, 2025 - L3Harris Technologies (NYSE: LHX) will release its second quarter 2025 financial results before the market opens on Thursday, Ju...
01/07/2025
WASHINGTON The Federal Communications Commission has rejected license challenges to three full-power Baltimore TV stations, renewing the licenses for Chesapeake...
01/07/2025
Dalet has released a new update to its Dalet Flex media workflow platform, introducing powerful new capabilities to its flagship platform....
01/07/2025
NEWARK, N.J. With the FIFA Club World Cup final rapidly approaching and the start of the 2026 FIFA World Cup now less than a year away, interest in soccer in th...
01/07/2025
COW Job Listing: Laser Engraved Logo
Brie Clayton July 1, 2025
0 Comments
Laser engraved logo
July 1, 2025Steffie Beltt's Mi Amor Music Video Cr...
01/07/2025
LeGrow.Studio Builds Broadcast Hub for ePro League
Brie Clayton July 1, 2025
0 Comments
TEM Constellation HD and BlackmagicURSA Broadcast G2 drive liv...
01/07/2025
Beeble launches SwitchLight 2.0, bringing AI-powered relighting to any footage
Brie Clayton July 1, 2025
0 Comments
New AI model delivers full-scene p...
01/07/2025
Steffie Beltt's Mi Amor Music Video Created with Blackmagic Design
Brie Clayton July 1, 2025
0 Comments
Blackmagic PYXIS 6K digital film camera...
01/07/2025
WASHINGTON The Federal Communications Commission's Enforcement and Media Bureaus have entered into a consent decree with Sinclair to resolve a variety of in...
01/07/2025
DENVER Low-power television (LPTV) station owners looking to navigate the complexities of selling their assets in todays dynamic media environment are invited t...
01/07/2025
NASA announced today that live programming from its NASA+ channel will be available on Netflix starting sometime this summer....
01/07/2025
WASHINGTON Federal Communications Commission Chair Brendan Carr has appointed Katie McAuliffe to serve as policy advisor in his office....
01/07/2025
MOUNTAIN VIEW, Calif. Alphabet's GFiber, the broadband provider formerly known as Google Fiber, has announced that it recently worked with Nokia to demonstr...
01/07/2025
NEW YORK, N.Y. DoubleVerify (DV) has announced the launch of DV Authentic Attention for Social. The product will first launch with Snap, the owner of Snapchat....
01/07/2025
WASHINGTON The Federal Communications Commission has rejected license challenges to three full-power Baltimore TV stations and agreed to renew the license for C...
01/07/2025
Compact new converter lets users capture live NDI and streaming sources into software over a USB interface
Video interface and IP workflow innovator Magewell ...
01/07/2025
Disguise, the award-winning tech company driving visuals for Broadway and West End hits including Redwood, Stranger Things: The First Shadow and Disney's Fr...
01/07/2025
Historic appointment ushers in unified leadership for WRAL-TV, New Media, and Digital Solutions
RALEIGH, N.C. - 6-27-25 - Capitol Broadcasting Company is prou...
01/07/2025
Back to All News
Feel the Beat: Glass Heart' Main Trailer and Title Song RevealedPlay Video
Play Video
Entertainment
01 July 2025
GlobalJapan
Link co...
01/07/2025
SVG New Sponsor Spotlight: Spyrosoft's Jonathan Witty on Futher Business Exp...
01/07/2025
The NIL Effect: How the Shifting Business of College Athletics Impacts On-Campus...
01/07/2025
Cherry on the cake: Inside the technical production of the Tour de France 2025 w...
01/07/2025
NESN's Josh Jun on Keeping Alternative Broadcasts Fresh for Boston Red Sox, ...
01/07/2025
TNT Sports Races Back Into NASCAR With Fresh Look, Familiar Edge Production approach emphasizes creative freedom, bold storytelling, casual-fan-friendly tone B...
01/07/2025
Back to All News
Watch: A Line Crossed: Netflix Drops Explosive Trailer for New...
01/07/2025
Tyngsboro, Mass. - June 30, 2025 - The 2025 ACM Annual Conference at Boston University was an energizing and inspiring gathering of community media professional...
01/07/2025
In many parts of the world, including major technology hubs in the U.S., there's a yearslong wait for AI factories to come online, pending the buildout of n...
30/06/2025
The Artemis II Space Launch System core stage is integrated with the solid rocket boosters inside High Bay 3 of the Vehicle Assembly Building at NASAs Kennedy S...
30/06/2025
RALEIGH, N.C. Capitol Broadcasting Co. has named Heather Gray vice president and general manager of WRAL-TV and WRAZ-TV here....
30/06/2025
The Virginia Association of Broadcasters has recognized Bill Sewell, Director of Engineering at WTKR & WGNT in Norfolk, Va. as the recipient of the 2025 J.J. Fr...
30/06/2025
The Society of Broadcast Engineers said its annual member drive resulted in the recruitment of 49 individual members....