N.C. State Researcher is Tracking the Parallel Pathways of Obesity, Diabetes and Inflammation

Written by: Jennifer Woodford, N.C. Research Campus

A generation ago, the prevailing opinion was that once a person became obese they would develop type 2 diabetes. Today, scientists like Dr. Slavko Komarnytsky, assistant professor of pharmacogenomics with N.C. State University’s Plants for Human Health Institute (PHHI) at the N.C. Research Campus in Kannapolis, know that obesity and diabetes are related but that the cause and effect are not quite so definite. Komarnytsky described the connection between the two diseases as “co-mingled and parallel.”

“At first we thought diabetes is coming from obesity,” he continued. “Now people are starting to realize that these are two different processes. They come together in many people, but that doesn’t mean it has to be there for everybody.”

Komarnytsky researches the genetic differences that cause obesity, diabetes and other metabolic disorders as part of his overall goal of finding new options for prevention and treatment of these diseases that are derived from plant-based bioactive compounds. Komarnytsky is finding that chronic inflammation, even at low levels, is a condition that connects the parallel pathways of obesity and diabetes and is a viable target for dietary supplements and therapeutic treatments.

Inflammation – Good and Bad

Every person experiences inflammation from swollen skin around a cut to joint pain after exercise. This type of inflammation serves as a warning and is part of the human body’s healing process.

“Bad things happen, when it goes out of control,” Komarnytsky said, “(and) when inflammation becomes a pathogenic process rather than your friend trying to heal or rebuild your tissues. When that system is broke (because of something) like excessive adipose tissue accumulation, our body reacts by trying to fix the issue. The way our body fixes things is to inflame the tissue so that microphages (white blood cells) can get in.”

Komarnytsky (pictured at left with lab technician Mickey Wilson, middle, and research specialist Dr. Debora Esposito, foreground) is uncovering plant-derived compounds that can counteract that activity and help reduce chronic inflammation in the human body.

Blueberries and Cabbage

In an institute of horticulturists and plant biologists, Komarnytsky is one of the few scientists who works with human cell cultures and animal studies. Komarnytsky’s expertise in cell culture as well as his facilities, which include a biosafety level 2 cell culture core lab, metabolic biology suite and analytical chemistry and biology suite, have opened up opportunities for international collaborations with scientists in Malaysia and South Africa.

But his central source of collaborations is within PHHI. Working with Dr. Mary Ann Lila, PHHI director, Komarnytsky is part of a project to understand how blueberry anthocyanins ameliorate inflammatory conditions in the gastrointestinal system. Funded by N.C. State’s Research and Innovation Seed Funding program, the project involves feeding lean and obese mice with physiological levels of anthocyanins incorporated into the diet and aims at improving gut health with anthocyanin amounts relevant to the normal human intake of fruits.

Komarnytsky also collaborates with PHHI’s Dr. Allan Brown, applied molecular geneticist and assistant professor in the Department of Horticultural Science, who uses traditional breeding methods to develop nutritionally-enhanced broccoli with higher levels of compounds like lutein, beta-carotene, sulforaphane and indole-3-carbinol, which are known to protect against cancer and other chronic diseases. Brown is in the early stages of developing isogenetic broccoli lines that are 99 percent genetically identical. The one percent difference is caused by increases in designated compounds. Brown and Komarnytsky have applied for a grant based on preliminary research findings to use the isogenic broccoli to further investigate the impact of these compounds on inflammation.

(L-R) Dr. Slavko Komarnytsky and Dr. Debora Esposito’s research shows that brassinosteroids found in plants like cabbage trigger responses in animal models similar to anabolic steroids.

Brassinosteriods, a natural steroid found in all plants but in higher concentrations in the Brassica genus that includes mustard greens, cabbage, broccoli, cauliflower and Brussels sprouts, are part of Komarnytsky’s research to understand muscles loss in relation to obesity, diabetes and inflammation. PHHI research specialist Dr. Debora Esposito found that ingestion of brassinosteroids in rat models reversed muscle loss by up to 20 to 30 percent within weeks of the treatment (view the article).

“You cannot reverse the process completely, but you can protect a lot of muscle tissue so the animal doesn’t lose as much muscle, and the muscle tissue they retain is healthier,” he said. “The muscle fibers are bigger. If you look at the distribution of specific fibers within the muscle, they are more like healthy muscle tissue than diseased.”

Komarnytsky emphasizes that the research is preclinical and that brassinosteriods have not been tested in humans. Another challenge is that brassinosteriods are found in small quantities in plants. “You’d have to eat pounds and pounds of cabbage in order to get a physiologically effective dose, but there are other possibilities,” he said.

Because brassinosteroids are complex compounds, synthesizing them is expensive. Komarnytsky is looking at new extraction methods and semi-synthetic approaches. “The next logical path is the toxicology testing in animals just to make sure they are safe. We know they are effective,” he commented.

Even though some of his research connects him to other countries, Komarnytsky’s focus remains in his lab tracking the parallel pathways of obesity, diabetes, other metabolic diseases and inflammation. He hopes that his research to identify and understand the health-promoting compounds in blueberries, broccoli and other vegetables that will reduce inflammation and restore muscles may one day create new and more beneficial products for consumers as well as more valuable crops for farmers to grow.

“We really try to dissect what is happening at the early stages of development of these diseases,” he said, “and try to understand how inflammation plays a part in the progression of both. There is much to be done with diet when it comes to inflammation and metabolic diseases. What we eat very much affects the state of our health. So if we add in nutrition that supports health while cutting out foods that promote disease, we can really change the course of our lives for the better.”

View the original article on the N.C. Research Campus website.