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Nov 06, 2014
 |  BC Innovations  |  Targets & Mechanisms

Greasing insulin

An entirely new class of fatty acids has just been discovered that potentially is more potent than the w-3 fatty acids found in fish oil. The new fatty acids-which work through G protein-coupled receptor 120, a target that had once been discarded by researchers-could be used to restore insulin sensitivity in patients with diabetes.1

G protein-coupled receptor 120 (GPR120; O3FAR1) was tapped as a potential obesity and diabetes target following a 2005 paper in Nature Medicine that showed the receptor triggered the release of glucagon-like peptide-1 (GLP-1) from intestinal cells when stimulated by unsaturated long-chain free fatty acids.2 But further studies showed that GPR120's direct effect on GLP-1 release would be minor or undetectable, and as a result companies abandoned the target in favor of related receptors that were able to stimulate insulin secretion.

In 2010, however, a team at the University of California, San Diego found that w-3 fatty acids-such as GlaxoSmithKline plc's Lovaza fish oil extract-exert their anti-inflammatory and insulin-sensitizing effects through GPR120.3 The receptor was shown to be highly expressed in mature adipocytes, where it helped increase glucose uptake, and in proinflammatory macrophages, where it decreased inflammatory responses.

Two years later, an international team showed that dysfunction of GPR120 led to obesity and obesity-associated metabolic disorders such as glucose intolerance and fatty liver.4

Despite the new angles presented by the target, there was one key problem-exogenous w-3 fatty acids are not very effective at activating GPR120. Now, a team at Harvard Medical School has identified fatty acids that operate through GPR120 and could be more potent correctors of glucose intolerance and insulin resistance than w-3 fatty acids.

The team, led by Barbara Kahn, started out by performing a comparative lipidomics analysis in...

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