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:

The role of vitamin A in diabetes
There has been no known link between diabetes and vitamin A -- until now.
Can continuous glucose monitoring improve diabetes control in patients with type 1 diabetes who inject insulin
Two studies in the Jan. 24/31 issue of JAMA find that use of a sensor implanted under the skin that continuously monitors glucose levels resulted in improved levels in patients with type 1 diabetes who inject insulin multiple times a day, compared to conventional treatment.
Complications of type 2 diabetes affect quality of life, care can lead to diabetes burnout
T2D Lifestyle, a national survey by Health Union of more than 400 individuals experiencing type 2 diabetes (T2D), reveals that patients not only struggle with commonly understood complications, but also numerous lesser known ones that people do not associate with diabetes.
Type 2 diabetes and obesity -- what do we really know?
Social and economic factors have led to a dramatic rise in type 2 diabetes and obesity around the world.
A better way to predict diabetes
An international team of researchers has discovered a simple, accurate new way to predict which women with gestational diabetes will develop type 2 diabetes after delivery.
The Lancet Diabetes & Endocrinology: Older Americans with diabetes living longer without disability, US study shows
Older Americans with diabetes born in the 1940s are living longer and with less disability performing day to day tasks than those born 10 years earlier, according to new research published in The Lancet Diabetes & Endocrinology journal.
Reverse your diabetes -- and you can stay diabetes-free long-term
A new study from Newcastle University, UK, has shown that people who reverse their diabetes and then keep their weight down remain free of diabetes.
New cause of diabetes
Although insulin-producing cells are found in the endocrine tissue of the pancreas, a new mouse study suggests that abnormalities in the exocrine tissue could cause cell non-autonomous effects that promotes diabetes-like symptoms.
The Lancet Diabetes & Endocrinology: Reducing sugar content in sugar-sweetened drinks by 40 percent over 5 years could prevent 1.5 million cases of overweight and obesity in the UK and 300,000 cases of diabetes
A new study published in The Lancet Diabetes & Endocrinology journal suggests that reducing sugar content in sugar sweetened drinks (including fruit juices) in the UK by 40 percent over five years, without replacing them with any artificial sweeteners, could prevent 500,000 cases of overweight and 1 million cases of obesity, in turn preventing around 300,000 cases of type 2 diabetes, over two decades.
Breastfeeding lowers risk of type 2 diabetes following gestational diabetes
Women with gestational diabetes who consistently and continuously breastfeed from the time of giving birth are half as likely to develop type 2 diabetes within two years after delivery, according to a study from Kaiser Permanente published today in Annals of Internal Medicine.

Related Diabetes Reading:

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

Bias And Perception
How does bias distort our thinking, our listening, our beliefs... and even our search results? How can we fight it? This hour, TED speakers explore ideas about the unconscious biases that shape us. Guests include writer and broadcaster Yassmin Abdel-Magied, climatologist J. Marshall Shepherd, journalist Andreas Ekström, and experimental psychologist Tony Salvador.
Now Playing: Science for the People

#513 Dinosaur Tails
This week: dinosaurs! We're discussing dinosaur tails, bipedalism, paleontology public outreach, dinosaur MOOCs, and other neat dinosaur related things with Dr. Scott Persons from the University of Alberta, who is also the author of the book "Dinosaurs of the Alberta Badlands".