Natural killer cells help to drive inflammation and insulin resistance

March 31, 2016, Joslin Diabetes Center

In obesity, the body's immune system can treat tissues as if they are suffering from a low-grade chronic infection. This obesity-induced inflammation is an important contributor to insulin resistance, a condition that can progress into type 2 diabetes. Researchers at Joslin Diabetes Center now have pinpointed a major inflammatory role for "natural killer" (NK) immune cells in abdominal fat—a type of tissue strongly implicated in insulin resistance.

Working in mice that were put on high-fat diets to model diabetes, "we demonstrated that obesity increases the expression of pro-inflammatory genes in abdominal fat, but not in other organs such as the liver or muscle, nor in subcutaneous fat," says Jongsoon Lee, PhD, Assistant Investigator in Joslin's Section on Pathophysiology and Molecular Pharmacology and Assistant Professor of Medicine at Harvard Medical School.

"Additionally, we showed that obesity increases the number and activity of NK cells in abdominal fat but not in other tissues," says Lee, senior author on a paper published online today in Cell Metabolism.

Working with Steven Shoelson, MD, PhD, Senior Investigator in the Section on Pathophysiology and Molecular Pharmacology and Professor of Medicine at Harvard Medical School, and other Joslin colleagues, Lee also discovered that in mice whose NK cells were removed, in abdominal fat is suppressed, and, most importantly, insulin resistance is improved. "Conversely, when we expanded the population of NK cells, we found that inflammation is increased, mainly in the , and insulin resistance is worsened," says Lee.

NK cells perform two main tasks for the . First, as their name suggests, they kill cells that have been infected or turned cancerous. Second, NK cells churn out many different forms of signaling proteins, which can promote or suppress inflammation by aiding in recruitment and activation of other .

Lee and his colleagues believe that NK cells help to regulate insulin resistance by releasing signaling proteins that affect the behavior of macrophages, another kind of immune cells. Macrophages that appear in fat are called "adipose tissue macrophages" (ATMs) and are thought to be the major players in controlling inflammation in obesity.

The Joslin team revealed that depleting NK cells decreases the number of ATMs, suppresses pro-inflammatory ATMs and increases anti-inflammatory ATMs. Moreover, expanding NK cells reverses these effects. While many types of immune cells are involved in obesity-induced inflammation, "NK cell modulations do not change any of the other immune cells," Lee says. "As such, we have established a strong indication between NK cells and ATMs in obesity."

Thus, in discovering that NK cells control ATMS and consequently inflammation, the Joslin scientists have identified a new mechanism in the development of obesity-induced insulin resistance in mouse models.

Lee notes that manipulating these NK cells could be a promising option for potential diabetes therapies, because people with type 2 diabetes show higher numbers of NK cells in their fat tissues. Although reducing the levels of these cells could be problematic due to their role in handling infections, he explains that the immune system generally works quite differently for the regulation of insulin resistance in obesity than it does for combating infections.

Lee's team is now looking to see if cutting the generation of certain inflammation-related proteins from NK or ATMs can reduce inflammation and in obesity.

Explore further: Study results suggest cell-free DNA may be involved in inflammation in obese patients

Related Stories

Study results suggest cell-free DNA may be involved in inflammation in obese patients

March 28, 2016
(Medical Xpress)—A team of researchers affiliated with multiple facilities in Japan has found that as fat cells die due to an increase in obesity, more cell-free DNA is released into tissue causing inflammation. In their ...

When the immune system promotes tumor growth

February 18, 2016
The immune system protects the body against cancer cells. The Elimination of cancer cells is an important task of NK cells. For NK cells to function properly, they require the activator STAT5.

Red ginseng, vitamin C may increase immune cell activity

March 3, 2016
(HealthDay)—Red ginseng and vitamin C enhance immune cell activation and suppress viral infection in mice, according to an experimental study published online Feb. 21 in the Journal of Pharmacy and Pharmacology.

Running helps mice slow cancer growth

February 16, 2016
Here's one more benefit of exercise: mice who spent their free time on a running wheel were better able to shrink tumors (a 50% reduction in tumor size) compared to their less active counterparts. Researchers found that the ...

Gamma-Delta T cells may play a role in insulin resistance and type 2 diabetes

January 5, 2015
New research in mice suggests that an unusual type of immune cell called "γδ T cells" may be a new drug and research target for treating or preventing type 2 diabetes caused by obesity. The research report, appearing in ...

A boost in microRNA may protect against obesity and diabetes

March 15, 2016
Obesity, which is associated with low-grade inflammation, is an important contributor in the development of diabetes and cardiovascular disease. While the role of several organs including adipose tissue have been implicated ...

Recommended for you

Separated entry and exit doors for calcium keep energy production smooth in the powerhouses of heart cells

September 18, 2018
Stress demands the heart to work harder and faster. To keep pace, the muscle must make its fuel at an accelerated rate. Bursts of calcium entering mitochondria—the cell's powerhouses—normally help control energy output, ...

First gut bacteria may have lasting effect on ability to fight chronic diseases

September 18, 2018
New research showing that the first bacteria introduced into the gut have a lasting impact may one day allow science to adjust microbiomes—the one-of-a-kind microbial communities that live in our gastrointestinal tracts—to ...

A new defender for your sense of smell

September 18, 2018
New research from the Monell Center increases understanding of a mysterious sensory cell located in the olfactory epithelium, the patch of nasal tissue that contains odor-detecting olfactory receptor cells. The findings suggest ...

Small molecule plays big role in weaker bones as we age

September 18, 2018
With age, expression of a small molecule that can silence others goes way up while a key signaling molecule that helps stem cells make healthy bone goes down, scientists report.

Sperm quality study updates advice for couples trying to conceive

September 17, 2018
Could doctors at fertility clinics be giving men bad advice? Dr. Da Li and Dr. XiuXia Wang, who are clinician-researchers at the Center for Reproductive Medicine of Shengjing Hospital in Shenyang in northeast China, think ...

Antioxidant found to be effective in treating mice with osteoarthritis

September 14, 2018
A team of researchers in Belgium and the Netherlands has found that feeding a common antioxidant to test mice was effective in treating osteoarthritis. In their paper published in Science Translational Medicine, the group ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.