Tracking Parallel Pathways of Obesity, Diabetes and Inflammation
A generation ago, the prevailing opinion was that once a person became obese they would develop type 2 diabetes.
Today, scientists like Slavko Komarnytsky, PhD, assistant professor of pharmacogenomics with NC State University (NCSU) Plants for Human Health Institute (PHHI) at the NC Research Campus (NCRC), 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.”
Inflammation isn’t the only consequence of accumulating excess adipose or fat tissue. “These layers of tissue are oxygen deprived, and don’t get nutrients as fast or efficient as they are supposed to. We understand now that fat is an endocrine organ just like your adrenaline glands that secretes hormones. Your fat tissue is also secreting other types of hormones, which tell your body how much metabolism to perform, how many calories you need to intake (and) how healthy the tissue is. All these signals come back and forth between your brain and your adipose tissue. So adipose tissue is not viewed any more as something inert. It’s rather like a separate organ and is quite active.”
Komarnytsky (pictured standing with Lab Technician Mickey Wilson, middle, and Research Scientist Debora Esposito, PhD, foreground) is uncovering plant-derived compounds that can counteract that activity and help reduce chronic inflammation in the human body.
Thunder God Vine
One of the botanical extracts that Komarnytsky studies is Tripterygium wilfordii or Thunder God Vine. It is native to Japan, Korea and China. According to the National Center for Complementary and Alternative Medicine, Thunder God Vine is used in Traditional Chinese Medicine to treat illnesses involving inflammation or over-activity of the immune system, such as rheumatoid arthritis, multiple sclerosis and lupus. Initial studies suggest that Thunder God Vine has potent anti-inflammatory qualities, but its high level of toxicity has prevented many human studies.
In mice, Komarnytsky witnessed “a little miracle” when he supplemented the high-fat diet of obese, diabetic mice with triptolide, a major bioactive principle of Thunder God Vine. “They still become obese, but they are completely fine. There is no sign of diabetes. Their blood glucose levels are normal and insulin tolerance is exactly where it is supposed to be,” he explained. “We are not trying to say that it is a cure for diabetes; by all means not, because the compound is quite toxic. What it gives us is a tool to dissect the disease, to be able to separate diabetes from obesity and try to understand the development of each of them and how they are related. Then maybe we can find a new generation of treatments.”
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 that 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 Malayasia and South Africa.
But his central source of collaborations is within PHHI. Working with Mary Ann Lila, PhD, PHHI director, Komarnytsky is part of a project to understand how blueberry anthocyanins ameliorate inflammatory conditions in the gastrointestinal system. Funded by NCSU Research and Innovation grant, 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.
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. Research Scientist Debora Esposito, PhD, who works in PHHI, found that in a rat model ingestion of brassinosteroid reversed muscle loss by up to 20 to 30 percent within weeks of the treatment.
“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. ”
For more information, visit the Plants for Human Health Institute.