SCIENTISTS have discovered a new class of molecules that protects humans from diabetes, and they are produced in human and mouse fat.
The researchers at the Salk Institute and Beth Israel Deaconess Medical Center (BIDMC) in Boston made the discovery after giving this new fat, or lipid, to mice with the equivalent of type 2 diabetes, with the elevated blood sugar being reduced in no time.
BIDMC researchers made the detailed scientific report on their achievement in the October 9 issue of Cell. Moreover, they found that the levels of these lipids are low among humans with a high risk for diabetes.
This, they said, suggests that the lipids could one day be utilized as a therapy for metabolic disorders.
Lipids, like cholesterol, have been demonized for being a leading cause of health problems.
However, recent research showed that some lipids, like the omega-3 fatty acids found in fish oils, are actually beneficial to human health.
The newly found lipids, called fatty acid hydroxy fatty acids (Fahfas), were lower among humans with early stages of diabetes and were much higher in mice resistant to diabetes.
“Based on their biology, we can add Fahfas to the small list of beneficial lipids,” said Alan Saghatelian, Salk professor at the Clayton Foundation Laboratories for Peptide Biology and one of the senior authors of the study.
“These lipids are amazing because they can also reduce inflammation, suggesting that we might discover therapeutic opportunities for these molecules in inflammatory diseases, such as Crohn’s disease and rheumatoid arthritis, as well as diabetes.”
Fahfas had eluded discovery for years since they are found in low concentrations, making them very difficult to find. However, with the use of the latest mass spectrometry techniques, Saghatelian and Barbara Kahn, vice chairman of the Department of Medicine at BIDMC and the other senior author of the work, uncovered the Fahfas when they analyzed the fat of a diabetes-resistant mouse model developed by Kahn.
“We engineered these mice to have more of a sugar transporter, called Glut4, in their fat because we had shown that when levels of this transporter are low, people are prone to developing diabetes,” Kahn said.
By examining how this sugar transporter might help protect against diabetes, the team noticed more fatty-acid synthesis among mice that had improved insulin activity and thus less likely to have diabetes.
“While many of the other lipids were essentially the same between normal mice and these diabetes-resistant mice, we saw these Fahfa lipids elevated by sixteen-fold among mice that were resistant to diabetes, standing out really clearly as a big change,” Saghatelian noted.
“After that, we elucidated their structures using a combination of mass spectrometry and chemical synthesis. We basically uncovered a whole new class of molecules using these techniques,” he stressed.
Once they identified Fahfas as being the lipid that was different between normal mice and these diabetes-resistant mice, they found something more significant—when the mice eat Fahfas, blood sugar levels dropped and insulin levels rose, indicating the potential therapeutic value of Fahfas.
To determine whether Fahfas are also relevant among humans or not, the team measured Fahfa levels among humans who are insulin-resistant, a condition which is often a precursor to diabetes, and found that their Fahfa levels were lower in fat and blood.
This suggested that changes in Fahfa levels might contribute to diabetes.
“The higher levels of these lipids seem to be associated with positive outcomes in mice and humans,” said Kahn, who is also a professor at Harvard Medical School.
“We showed that the lipids work through multiple mechanisms. When blood sugar is rising, such as after a meal, the lipids rapidly stimulate secretion of a hormone that signals the pancreas to secrete insulin. In addition, these novel lipids also directly stimulate sugar uptake into cells and reduce inflammatory responses in fat tissue and throughout the body,” she said.