The new research shows elevated levels of a receptor present on leucocytes of the innate immune response in people at risk for these chronic diseases. The receptors are the body's first line of defense against infectious invaders, and they trigger a rush of cytokines, the body's aggressive immune soldiers, into the bloodstream.
The research, published in the journal Diabetes Care on Feb. 22, studied individuals diagnosed with metabolic syndrome -- a cluster of cardio-metabolic risk factors linked to many life-threatening diseases. Metabolic syndrome is found in about a third of American adults and people in other industrialized countries.
The syndrome is a high-risk obesity state as previously shown by diabetes expert Ishwarlal Jialal and his team at the UC Davis Medical Center. It increases the risk of developing diabetes at least five-fold and heart disease by two- to four-fold. Jialal, professor of pathology and laboratory medicine at UC Davis Health System, also led the new study.
The receptors, or sensors, on cells are called Toll-like receptors (TLRs), and the Nobel Prize was awarded last year for discoveries that showed they initiate the swift innate immune response to infections. But the inflammation they trigger can also be harmful. In mice it has been shown that two TLRs -- TLR2 AND TLR4 -- are important in the development of both diabetes and heart disease.
These receptors are present in many cells, but they are most abundant on monocytes, a type of white blood cell that plays a central role in the inflammation response to invading microbes. They can be triggered by pathogen products or signals from dying cells and saturated fatty acid.
The UC Davis research focused on TLR2 and TLR4. For the study, researchers evaluated 90 individuals between the ages of 21 and 70, of whom 49 had at least three features characteristic of metabolic syndrome. These included hypertension, low HDL-cholesterol, high triglycerides and obesity, as evidenced by increased waist circumference, or a glucose level between 101-125 mg/dl but not indicative of diabetes. Members of the control group had no more than two such markers. People with atherosclerosis, diabetes, inflammatory or malignant disease, and other disorders were excluded to study the receptor function without confounding variables, and to gain insights into nascent or early metabolic syndrome prior to complications.
Comparisons of the blood of participants from both groups showed that the metabolic syndrome group exhibited significantly higher levels of both messenger RNA and cell-surface receptor proteins TLR2 and TLR4, increased levels of the master switch of inflammation in the nucleus, and a much higher concentration of immune soldiers in the blood, such as cytokines, that create inflammation.
All of these abnormalities were independent of obesity, suggesting they are due to the metabolic-syndrome environment. The levels of both free fatty acids and the product of gram-negative bacteria endotoxin also were increased in the blood of individuals with metabolic syndrome at least two- and three-fold respectively, and explained in part the TLR4 increase.
The research suggests that suppressing TLR activity with weight loss and with diet, exercise and drugs targeted specifically at these receptors, might prove effective in treating heart disease, diabetes and other conditions linked to metabolic syndrome.
Jialal pointed out that not all obese people suffer from the constellation of symptoms that make up metabolic syndrome, and in fact, about 30 percent of obese people are at low risk for metabolic complications, according to one key study. But since research shows increased inflammation in obese people, the Toll-like receptor and monocyte findings may help define individuals at high risk for obesity.
Jialal's research group reported last year that monocytes and related macrophages were present in the fat of individuals with metabolic syndrome and that their fat was more inflamed. The new finding shows that the Toll-like sentinel proteins might be directing an increase in this activity, and that the inflammatory agents are making it into the bloodstream, from where they can go to any part of the body, including fat, liver and heart.
The research is funded by the American Diabetes Association.
UC Davis Health System is improving lives and transforming health care by providing excellent patient care, conducting groundbreaking research, fostering innovative, interprofessional education, and creating dynamic, productive partnerships with the community. The academic health system includes one of the country's best medical schools, a 631-bed acute-care teaching hospital, an 800-member physician's practice group and the new Betty Irene Moore School of Nursing. It is home to a National Cancer Institute-designated cancer center, an international neurodevelopmental institute, a stem cell institute and a comprehensive children's hospital. Other nationally prominent centers focus on advancing telemedicine, improving vascular care, eliminating health disparities and translating research findings into new treatments for patients. Together, they make UC Davis a hub of innovation that is transforming health for all. For more information, visit healthsystem.ucdavis.edu.
Carole Gan | EurekAlert!
Researchers release the brakes on the immune system
18.10.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn
Norovirus evades immune system by hiding out in rare gut cells
12.10.2017 | University of Pennsylvania School of Medicine
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
20.10.2017 | Interdisciplinary Research
20.10.2017 | Materials Sciences
20.10.2017 | Earth Sciences