Dhurandhar is an alum of the University of Mumbai.
AB Wire
NEW YORK: Dr. Nikhil Dhurandhar, professor and chairman of the Department of Nutritional Sciences at Texas Tech University, who received almost $3 million from Vital Health Interventions while at Pennington Biomedical Research Center at Louisiana State University and subsequently brought it to his present position, is close to a drug that will change the way diabetes is treated.
Dhurandhar says his research is based on human adenovirus 36, which causes obesity in humans and animals while at the same time reducing blood sugar, a phenomenon Dhurandhar first noticed years ago in rodent models.
“It’s a little paradoxical because you have an agent that is making an animal fatter, so you would expect their glucose levels to deteriorate,” he said, according to Texas Tech news release.
Dhurandhar, who is president of The Obesity Society and one of the pioneers of the infectobesity movement, came to Texas Tech in November. He has been studying viral obesity for years, which he started when he was a physician in India focusing on patients with obesity. His research related to this virus focuses on diabetes treatment and creating a vaccine for viral obesity. Dhurandhar holds a number of patents for his work on adenovirus 36. He did his Ph.D. from the University of Mumbai.
He isolated a protein from adenovirus 36 responsible for reducing blood sugar and tested it on both diabetic cells and animals. Both experiments showed the protein improved diabetes, and other researchers doing similar experiments confirmed Dhurandhar’s results. The next step is developing a drug that eventually will be tested on humans, which, if successful, could be a significant step forward in treating diabetes.
Diabetes occurs when glucose builds up in the blood instead of being used by cells for energy production. In a normal circulatory system, glucose molecules in the bloodstream will enter the fat and muscle cells that line the blood vessels. Insulin, a hormone, is needed to start the molecular reaction that pulls the glucose into the cells.
A Type 1 diabetic doesn’t produce insulin. Type 2 diabetes is known as insulin resistant; the body produces insulin but is ineffective in promoting glucose intake by the body’s cells. In both types of diabetes, glucose can build up in the blood at dangerous levels. Providing insulin or drugs that promote the action of insulin are some of the main approaches to decrease glucose levels in the blood, thus treating diabetes. The adenovirus protein Dhurandhar and his research team identified reduces blood glucose levels in the absence of insulin and without mimicking the action of insulin.
Diabetes also affects the liver. The human body needs glucose all the time, which is provided by food. Normally, some of the surplus glucose is stored in the liver. This stored glucose is released when a person is not eating, and the release is terminated when a person is eating. In diabetes, this release of glucose is uncontrolled, thus contributing to an increase in blood glucose levels.
This protein also blocks uncontrolled glucose from liver cells, Dhurandhar said, which would contribute to lower blood sugar.
“The beauty of this is this protein acts independent of insulin. Hence, the drug we develop may work for Type 1 because it will act in the absence of insulin, or it could work in Type 2 in the presence of insulin resistance,” he said.
He is optimistic the protein will have similar effects on humans as it has shown in other organisms.
Dhurandhar, who coined the term “Infectobesity”, has received research funding from the NIH, American Diabetes Association, Federal Emergency Management Agency, and other non-profit or commercial funding sources, has published over 100 scientific articles, and book chapters, and served as a mentor or advisor for several students and postdoctoral fellows.
Obesity is a term very familiar to Dhurandhar. His father is considered the father of obesity practice in the Indian medical community, and when he went to medical school, Dhurandhar knew his passion was in obesity treatment.
“I often saw the difficulties that people suffering from obesity face and how quacks take them for a ride,” he told Texas Tech. “I pondered about what could be done for them.”
He added: “There is much more to nutrition than obesity,” he said. “Also, there is more to obesity than nutrition. Both are true.”
Dhurandhar took a hiatus from his medical practice to come to the United States in the 1980s for a master’s degree in nutrition, then returned to Bombay, India, for a doctorate in biochemistry. While there he heard a lecture from S.M. Ajinkya, a well-known veterinary pathologist, who talked about an avian virus killing thousands of chickens a day. These chickens died fat instead of emaciated.
Dhurandhar wondered how chickens infected with a deadly virus could be gaining weight.
“I reasoned, if a bird dies of a viral infection it should have no fat, and you’re describing plenty of fat,” Dhurandhar remembers asking. “Is this virus making those chickens fat?
“What Dr. Ajinkya said in response changed everything. He said, ‘I don’t know.’ Then he said, ‘You’re doing a Ph.D. Why don’t you find out?’”
Dhurandhar performed three experiments with this adenovirus, the first two with chickens and the third involving humans. He found that, after injecting chickens with the virus, they gained weight in just a few weeks.
While he couldn’t inject humans with the virus for ethical reasons, he obtained blood samples from patients who came into his clinic for obesity treatment and discovered that about 20 percent of the patients had antibodies for the virus, which meant they’d been infected at some point. The three experiments indicated this virus did cause obesity in animals and humans infected with it.
The studies showed another, less expected, relationship. Dhurandhar said typically symptoms like high blood sugar, high cholesterol and high triglycerides accompany obesity. However, both the chickens and the humans who’d had the virus were obese but had low cholesterol and low triglycerides, suggesting an association between the virus and a patient’s metabolic health.
Previously, the cause of obesity was limited to food choices and inactivity.
The cause of obesity, according to all the key players, was limited to two things: eating too much and exercising too little. Today, the American Medical Association and other organizations have declared obesity a disease, and the mindset is changing. Twenty years ago scientists weren’t looking for theories or viruses; they had calorie counts.
This made finding a U.S. lab to support Dhurandhar’s research in viruses and obesity difficult. Dhurandhar sent letters and made phone calls to research labs throughout the United States, looking for someone interested in his research. When no one responded favorably, he took a postdoctoral fellowship in any area, ending up at North Dakota State University in Fargo. For two years he studied the biochemistry of sunflower pectin enzymes and wrote hundreds of letters seeking a lab that would allow him to engage in researched related to infections and obesity.
After one year and 11 months, after he and his wife decided to return to India and secured their son’s school tuition in Bombay, he got a call from a researcher at the University of Wisconsin inviting Dhurandhar to join his lab.
Once there, he found he couldn’t import the Indian adenovirus he’d originally experimented with, so he picked up the catalog to find a different virus. There were 50 different viruses. Going with his gut, he picked No. 36 and replicated his Indian experiments.
“The very first experiment showed the human adenovirus Ad36 fattened chickens but reduced their cholesterol and triglycerides, just like the Indian virus,” he said. “Ad36 clicked.”
He replicated the experiment in a number of different animal models including rats, mice and monkeys, with the same results. Over time, the scientific and medical communities accepted Dhurandhar’s conclusions, and the field of infectobesity was born. His research also contributed to the realization that obesity is more complicated than overall caloric intake.
“In my opinion the word obesity is sort of misleading,” he said. “The actual word should be obesities because there are so many different types.
“There are multiple contributors to the obesity epidemic. We generally tend to focus on eating too much and not moving enough.”
Today, Dhurandhar’s research is split between obesity and diabetes, both related to this obesity-causing virus. He applied the evidence-based association between the virus and lower blood sugar and cholesterol to diabetes, of which high blood sugar is a symptom. He is working to isolate the protein in the virus that improves metabolic numbers so it can be administered to diabetics to lower their blood sugar.