The discovery of a new class of lipid molecules that enhance insulin sensitivity and blood sugar control offers a promising new avenue for the prevention and treatment of type 2 diabetes. A team of scientists from Beth Israel Deaconess Medical Center (BIDMC) and the Salk Institute discovered this new class of molecules.
Senior team leader Dr. Barbara Kahn, who is also vice chair of the Department of Medicine at BIDMC and the George R. Minot Professor of Medicine at Harvard Medical School, grew up in Kansas City and graduated from the Barstow School Academy. She has family here, including her mother and two brothers, nieces and nephews, and she visits several times a year.
“We were blown away to discover this completely new class of molecules,” Kahn said.
Named fatty acid esters of hydroxy fatty acids, or FAHFAs, these new lipids are in fat cells as well as other cells throughout the body. They now join a small group of fatty acids known to benefit health, which also include omega-3 fatty acids found in fish oil. Unlike omega-3 fatty acids, which are not made in mammals, FAHFAs are actually produced inside the human body.
“This important feature gives FAHFAs an advantage in terms of therapeutic development because we can potentially modify the rate of production and breakdown throughout the body,” noted Kahn.
“We studied the biologic effects of just one family member of this type of molecule. There are 23 other family members and we will determine which ones are most beneficial. We need to find out how these molecules are made in our tissues and how they are broken down because [FAHFA] levels are low in people at high risk for, and those who already have, diabetes. If we raise the levels, we may be able to treat or prevent diabetes,” Kahn said.
Kahn said the project has been in the works since the early ‘90s when she and her team used “genetically engineered mice to recapitulate situations in humans with type 2 diabetes. We made transgenic mice so we could understand causes of type 2 diabetes and develop treatment strategies,” Kahn said.
Over the next 15-plus years, Kahn and her co-authors conducted a series of experiments and discovered that feeding mice extra FAHFAs resulted in a rapid and dramatic drop in blood sugar and rise in insulin. They also looked at FAHFA levels in human fat and plasma, studying samples from individuals who were known to be insulin resistant and at high risk for developing diabetes. In this case, FAHFA levels were found to be lower than levels in people with normal insulin sensitivity, suggesting that changes in FAHFA levels might be contributing to diabetes.
“Fat tissue is much more important than we originally thought,” Kahn said. “A certain amount of fat is important. It makes hormones that are not found in other tissues. These fat-derived hormones regulate energy expenditure and help the body to handle sugar by stimulating sugar uptake from the blood into muscle cells and reducing the release of sugar from the liver. Adipose [fat] cells are important for metabolic balance.”
Kahn explained that her team previously showed that increased conversion of glucose into lipids in fat cells improves metabolic balance.
“So we wanted to find out what fatty acids were synthesized in the mice that had more sugar transporters in fat cells and thus were protected from diabetes,” she said.
The discovery of FAHFAs is good because they lower blood sugar. But Kahn and her team have also found them to be potentially beneficial in fighting other diseases due to their anti-inflammatory effects.
“We are in discussions to schedule human clinical trials and because these molecules exist in our bodies and in our foods, we hope to get approval for the study more quickly than if we were testing synthetic drugs,” Kahn said.
“This [discovery] is of critical importance as rates of obesity and type 2 diabetes remain at epidemic proportions worldwide,” Kahn said.
The scientific article Kahn and her team published is in the Oct. 9, 2014, issue of Cell.
