Corporate Banner
Satellite Banner
Scientific Community
Become a Member | Sign in
Home>News>This Article

Succinate Levels Linked to Immune Response and Inflammation

Published: Tuesday, May 07, 2013
Last Updated: Tuesday, May 07, 2013
Bookmark and Share
Metabolic intermediate plays major role in alerting the immune system - measuring succinate levels may prove effective diagnostic tool in cancer.

Along the path from food to energy, intermediate molecules emerge that form the starting materials for the next step. Traditionally, these intermediates were viewed simply as building blocks — essential for the process, but otherwise inert.

But recently, a team of researchers including senior associate member Ramnik Xavier and Clary Clish, director of the Broad’s Metabolite Profiling Platform, revealed that one of these metabolic intermediates, known as succinate, plays a key role in alerting the body’s immune system — and may provide a crucial link between chronic inflammation, autoimmune disease, and cancer.

“Succinate is an important danger signal. It’s a good marker for cell stress,” said Xavier, a co-senior author of the study, recently published in Nature. The study linked high-levels of succinate to the production of an immune protein that triggers inflammation. Because succinate can be measured in blood, this finding may open the door to new diagnostics that measure immune responses.

The foundation for this discovery was laid by senior author Luke O’Neill, a professor at Trinity College in Dublin, who first observed that certain metabolic pathways in immune cells became highly active after the cells were stimulated with bacteria. The triggering of these pathways suggested the immune cells might be shifting their metabolism in a way previously thought to be exclusive to cancer cells.

One of the hallmarks of cancer cells is their ability to break down glucose at a vastly higher rate than normal cells. While most cells rely on oxygen to break down food, cancer cells can also ferment glucose — a less efficient process that does not require oxygen — to generate fuel. This metabolic shift allows them to adapt to the oxygen-deficient conditions inside tumors. The phenomenon, known as the Warburg effect, enables rapidly dividing tumor cells to generate the essential biological building blocks they need to grow. O’Neill also noted high levels of succinate in these same immune cells, and wondered what role this intermediate product might be in the metabolic shift.

Xavier, who specializes in the study of autoimmune disease, was intrigued. He offered to establish a collaborative effort with scientists at the Broad to help identify the biological circuit that might enable this metabolic shift and cause the accumulation of succinate.

Working with Xavier, Clish and the members of the Broad’s Metabolite Profiling Platform discovered that the high levels of succinate were a result of the shift and lead to an increase in the production of interleukin 1-beta, an immune protein linked to pain, inflammation, and autoimmune disease.

“Multiple studies have shown that chronic inflammation is a precursor event for several epithelial cancers,” says Xavier. “This is evidence that some of the same pathways that accelerate the progression of tumors are also operational in innate immunity.” What’s more, Xavier believes that succinate may not be the only the immune signal that plays a role in disease. Together, Xavier, Clish, and O’Neill are expanding their research to include other immune signals.

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Researchers Develop a New Means of Killing Harmful Bacteria
Engineered particles are capable of producing toxins that are deadly to targeted bacteria.
Friday, June 26, 2015
Broad Institute & Google Genomics Combine Bioinformatics and Computing Expertise
Both companies explore how to break down major technical barriers that increasingly hinder biomedical research.
Thursday, June 25, 2015
Scientists Make Connection Between Genetic Variation and Immune System
Researchers demonstrate how genetic variations can influence immune cell function.
Tuesday, May 13, 2014
Taking Immune Cells for a Test Drive
Combining biological experimentation on human white blood cells with advanced computational methods can help explain the functional impact of human genetic variation on immune disease.
Monday, March 17, 2014
Charting Microbial Ecosystem of Crohn’s Disease
Study analyzed the microbiomes of 447 newly-diagnosed patients with Crohn’s and 221 healthy individuals.
Thursday, March 13, 2014
Circuitry of Cells Involved in Immunity, Autoimmune Diseases Exposed
Connections point to interplay between salt and genetic factors.
Tuesday, June 18, 2013
Surveying Cells, One At a Time
When studying any kind of population — people or cells — averaging is a useful, if flawed, form of measurement.
Wednesday, May 22, 2013
Scientific News
Developing Drug Resistance may be a Matter of Diversity for Tuberculosis
Researchers have probed the bacteria that causes tuberculosis, Mycobacterium tuberculosis, to learn more about how individual bacterial cells change and adapt while in the human body.
Surprising Trait Found in Anti-HIV Antibodies
Scientists at The Scripps Research Institute (TSRI) have new weapons in the fight against HIV.
Some Gut Microbes May Be Keystones of Health
University of Oregon scientists have found that strength in numbers doesn’t hold true for microbes in the intestines. A minority population of the right type might hold the key to regulating good health.
Essential Component of Antiviral Defense Identified
Infectious disease researchers at the University of Georgia have identified a signaling protein critical for host defense against influenza infection.
Single Vaccine for Chikungunya, Related Viruses May be Possible
What if a single vaccine could protect people from infection by many different viruses? That concept is a step closer to reality.
Is Allergy the Price We Pay for Our Immunity to Parasites?
New findings help demonstrate the evolutionary basis for allergy.
Blocking the Transmission Of Malaria Parasites
Vaccine candidate administered for the first time in humans in a phase I clinical trial led by Oxford University’s Jenner Institute, with partners Imaxio and GSK.
Mucus – the First Line of Defence
Researchers reveal the important role of mucus in building a good defence against invaders.
Antibody Targets Key Cancer Marker
University of Wisconsin-Madison researchers have created a molecular structure that attaches to a molecule on highly aggressive brain cancer and causes tumors to light up in a scanning machine.
Gene-Edited Immune Cells Treat ‘Incurable’ Leukaemia
A new treatment that uses ‘molecular scissors’ to edit genes and create designer immune cells programmed to hunt out and kill drug resistant leukaemia has been used at Great Ormond Street Hospital (GOSH).

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos