Scientists at the Salk Institute in La Jolla and Beth Israel Deaconess Medical Center in Boston announced Thursday they have discovered a new class of molecules — produced in human and mouse fat — that protect against diabetes.
The researchers found that giving this new fat, or lipid, to mice with the equivalent of type 2 diabetes lowered their elevated blood sugar, as detailed in the journal Cell. The team also found that levels of the new lipids are low in humans with a high risk for diabetes, suggesting that the lipids could potentially be utilized as a therapy for metabolic disorders.
Lipids, like cholesterol, are typically associated with poor health. But in recent years, researchers have discovered that not all lipids are bad for you, such as the much touted omega-3 fatty acids that are found in fish oils.
The newly discovered lipids, called fatty acid hydroxy fatty acids, or FAHFAs, were lower in 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,” says Alan Saghatelian, Salk professor in the Clayton Foundation Laboratories for Peptide Biology and one of the senior authors of the work. “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 not been noticed previously in cells and tissues because they are present in low concentrations, making them difficult to detect. Using the latest mass spectroscopy techniques, Saghatelian and Barbara Kahn, vice chair of the Department of Medicine at Beth Israel and the other senior author of the work, uncovered the FAHFAs when they examined the fat of a diabetes-resistant mouse developed by Kahn.
To determine whether FAHFAs are also relevant in humans, the team measured FAHFA levels in 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, suggesting that changes in FAHFA levels may contribute to diabetes.
“The higher levels of these lipids seem to be associated with positive outcomes in mice and humans,” says Kahn, who is also a professor at Harvard Medical School. “We show 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.”
These combined effects make the therapeutic potential of the lipids tremendous, say the researchers. Aside from existing in low levels within a wide range of vegetables, fruits and other foods, FAHFAs are also — unlike the other known beneficial lipids — produced and broken down inside the body. Potentially, new drugs could target the pathways that make or break down lipids to control FAHFA levels.
The Salk Institute for Biological Studies is one of the world’s preeminent basic research institutions. Founded in 1960 by polio vaccine pioneer Jonas Salk, the institute is an independent nonprofit organization and architectural landmark.
– From a Salk Institute press release
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