Discovery Of “Good Fat” Molecules Could Lead To New Diabetes Treatment

While the word “fat” has many negative connotations, some fats are essential to survival and have beneficial attributes. A team of researchers have just discovered a class of naturally occurring lipids that could be used to develop new treatments for diabetes and inflammatory disease. The research was led by Mark Yore and Ismail Syed of Beth Israel Deaconess Medical Center (BIDMC) in Boston and the research was published in Cell

The newly discovered class of lipids, dubbed fatty acid hydroxyl fatty acids (FAHFAs), eluded scientists for so long because they are only found in small concentrations within cells. After analyzing their structure, the team discovered that that they are actually considered to be “good fats.”

Barbara Kahn, co-senior author from BIDMC, had created a mouse model with increased levels of Glut4, a sugar transporter. This made the mice resistant to diabetes. Closer examination of this process revealed that those with lower blood sugar due to increased insulin made more of a never-before-seen fatty acid, now known as FAHFAs. 

The team also found that the mice who are diabetes resistant have FAHFA levels about sixteen times higher than ordinary mice. In order to test whether this relationship was causative, the normal mice were fed a diet containing FAHFAs. Surprisingly, insulin levels increased and blood sugar dropped, which are important factors in controlling or preventing diabetes. 

FAHFAs are not just found in mice engineered to be resistant to diabetes. They’re also found in the human body and in several foods including beef, egg yolk, apples, and poultry. In fact, humans with insulin resistance, a diabetes precursor, had FAHFA levels only 25 to 50% of those in people with normal insulin function.

Graphical abstract of the team’s research. Image credit: Yore et al., 2014

“Higher levels of these lipids seem to be associated with positive outcomes in mice and humans,” Kahn said in a press release. “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.”

The next step of the research will be to pin down the mechanism involved and verify that FAHFA produces a signal that causes the release of insulin. If this can be determined, it could lead to new treatments. Even if the fats cannot be given directly as a therapy, they could inspire synthetic medications to help boost insulin and decrease blood sugar. Anti-inflammatory properties of the FAHFAs could be used to help treat diseases like Crohn’s or rheumatoid arthritis. Additionally, as those who are at-risk for these diseases have lower FAHFA levels than normal, it could be used as a marker to predict disease for early intervention.

“Because we can detect low FAHFA levels in blood before a person develops diabetes, these lipids could serve as an early marker for diabetes risk,” added Kahn. “We want to test whether restoring the lipids before diabetes develops might potentially reduce the risk or even prevent the disease.”

 

 

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