Nav: Home

Discovery reveals how obesity causes disease -- and two ways to stop it

July 23, 2018

New research from the University of Virginia School of Medicine explains why obesity causes harmful inflammation that can lead to diabetes, clogged arteries and other health problems. Doctors may be able to use this knowledge to battle these chronic diseases and others driven by damaging inflammation.

"All these diseases have a common denominator," said researcher Vlad Serbulea, PhD. "It may well be that we've identified what starts off the whole cascade of inflammation and metabolic changes."

Effects of Obesity

The researchers, for the first time, were able to explain why resident immune cells in fat tissue - immune cells that are thought to be beneficial - turn harmful during obesity, causing unwanted and unhealthy inflammation.

The research team, led by Norbert Leitinger, PhD, of UVA's Department of Pharmacology, found that damaging "free radicals" produced within our bodies react with substances known as lipids inside fat tissue. This attack on the lipids prompts them to cause inflammation, a natural immune response.

"Free radicals are so reactive that they want to hitch onto something," Serbulea explained. "Lipids happen to be a very good sink for these radicals to combine with."

That results in a process called "lipid oxidation." At first the scientists expected the oxidized lipids would prove harmful, but it wasn't that simple. Some of the oxidized lipids were causing damaging inflammation - reprogramming immune cells to become hyperactive - but other oxidized lipids were present in healthy tissue. Specifically, shorter "truncated" ones are protective, while longer "full-length" ones were inflammatory.

"When we compare healthy and obese tissue, what seems to change is the ratio of full-length and truncated oxidized lipids," Serbulea said. "Our studies show that the full-length, or longer, oxidized lipids are quite inflammatory. They promote inflammation within these immune cells, and we think that instigates and perpetuates the disease process within [fat] tissue during obesity."

A Drug to Combat the Inflammation of Obesity

Now that scientists know which oxidized lipids are causing problems, and how, they can seek to block them to prevent inflammation. They may be able to develop a drug, for example, that would reduce the number of harmful, full-length oxidized lipids.

"Now, knowing that some of these molecules are really bad guys, so to speak, eliminating them from the circulation may have a very beneficial effect on chronic diseases," said Leitinger, of UVA's Robert M. Berne Cardiovascular Research Center and UVA's Carter Immunology Center.

Alternately, doctors might want to promote the number of beneficial, shorter phospholipids. "Inflammation is important for your body's defenses, so you don't want to eliminate it completely," Leitinger said. "It's a question of finding the right balance."

By restoring that balance, doctors may be able to make significant inroads against chronic diseases that now plague millions of people.

"One thing we showed is that metabolism in the immune cells is an exploitable target," Serbulea said. "It's been a target in diseases like cancer, but now for obesity and atherosclerosis it becomes more and more of a focus."
-end-
Findings Published

The researchers have published their findings in PNAS, the Proceedings of the National Academy of Sciences. The research team consisted of Serbulea, Clint Upchurch, Michael Schappe, Paxton Voigt, Dory DeWeese, Bimal Desai, Akshaya Meher and Leitinger.

The work was supported by the National Institutes of Health (grants R01 DK096076, P01 HL120840 and R01 GM108989) and a University of Virginia Double-Hoo Research Award.

To keep up with the latest medical research news from UVA, subscribe to the Making of Medicine blog at makingofmedicine.virginia.edu.

University of Virginia Health System

Related Diabetes Articles:

Maternal gestational diabetes linked to diabetes in children
Children and youth of mothers who had gestational diabetes during pregnancy are at increased risk of diabetes themselves, according to new research published in CMAJ (Canadian Medical Association Journal).
Two diabetes medications don't slow progression of type 2 diabetes in youth
In youth with impaired glucose tolerance or recent-onset type 2 diabetes, neither initial treatment with long-acting insulin followed by the drug metformin, nor metformin alone preserved the body's ability to make insulin, according to results published online June 25 in Diabetes Care.
People with diabetes visit the dentist less frequently despite link between diabetes, oral health
Adults with diabetes are less likely to visit the dentist than people with prediabetes or without diabetes, finds a new study led by researchers at NYU Rory Meyers College of Nursing and East Carolina University's Brody School of Medicine.
Diabetes, but not diabetes drug, linked to poor pregnancy outcomes
New research indicates that pregnant women with pre-gestational diabetes who take metformin are at a higher risk for adverse pregnancy outcomes -- such as major birth defects and pregnancy loss -- than the general population, but their increased risk is not due to metformin but diabetes.
New oral diabetes drug shows promise in phase 3 trial for patients with type 1 diabetes
A University of Colorado Anschutz Medical Campus study finds sotagliflozin helps control glucose and reduces the need for insulin in patients with type 1 diabetes.
More Diabetes News and Diabetes Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Erasing The Stigma
Many of us either cope with mental illness or know someone who does. But we still have a hard time talking about it. This hour, TED speakers explore ways to push past — and even erase — the stigma. Guests include musician and comedian Jordan Raskopoulos, neuroscientist and psychiatrist Thomas Insel, psychiatrist Dixon Chibanda, anxiety and depression researcher Olivia Remes, and entrepreneur Sangu Delle.
Now Playing: Science for the People

#537 Science Journalism, Hold the Hype
Everyone's seen a piece of science getting over-exaggerated in the media. Most people would be quick to blame journalists and big media for getting in wrong. In many cases, you'd be right. But there's other sources of hype in science journalism. and one of them can be found in the humble, and little-known press release. We're talking with Chris Chambers about doing science about science journalism, and where the hype creeps in. Related links: The association between exaggeration in health related science news and academic press releases: retrospective observational study Claims of causality in health news: a randomised trial This...