Numerous studies in animals and humans have demonstrated anti-inflammatory and anti-diabetic activity of omega-3 fatty acids. Now, researchers at the University of California, San Diego, have discovered a receptor, GPR120, on immune cells and on fat cells that bind to omega-3s. They found that inflammatory immune cells were inhibited by omega-3s as long as they expressed the GPR120 receptor on their surface. The researchers also supplemented the diet of obese diabetic mice with omega-3s and were able to reverse the insulin resistance associated with their diabetes. When these mice were engineered not to express GPR120, omega-3 fatty acids could not reverse insulin resistance, showing that omega-3s mediate the anti-diabetic activity through the GPR120 receptor.
When saturated fats activate receptors on fat cells and immune cells, called macrophages, pro-inflammatory substances are released. In contrast, unsaturated fats are usually inactive, but evidence is accumulating that the unsaturated omega-3 fatty acids are anti-inflammatory. Omega-3s comprise three different fatty acids: alpha-Linoleic acid (ALA), Eicosapentaenoic acid (ELA), and Docosahexaenoic acid (DHA). ALA is an essential nutrient, which means that our bodies cannot make it and we have to get it from food. ELA and DHA can be synthesized by our bodies from ALA or obtained from food. Fish oil and other foods contain different proportions of the three omega-3s.
How omega-3s suppress inflammation
The research team, headed by Jerold Olefsky, an endocrinologist at the University of California, found that when macrophages, which are immune cells that mediate inflammation, were treated with the omega-3 fatty acid DHA, all inflammatory function was shut down. DHA appeared to bind to the GPR120 receptor on these cells. When cells were generated without the GPR120 receptors and then treated with DHA, all inflammatory pathways remained open. This suggested that GPR120 was needed for omega-3s` to inhibit inflammation.
How omega-3s prevent type 2 diabetes
A chronic low level of inflammation is linked to insulin resistance or decreased insulin sensitivity. This kind of inflammation is caused by immune cells migrating to fat tissue and the liver, where they become activated and secrete pro-inflammatory substances. The researchers found high levels of the GPR120 receptor on these activated macrophages and on fat cells. To determine if omega-3s (DHA and EPA) could prevent insulin resistance in mice through the anti-inflammatory effect mediated by GPR120, researchers used genetically modified mice lacking the GPR120 receptor and unmodified mice. They fed both groups a high fat diet, supplemented with omega-3s. The mice lacking GPR120 developed severe insulin resistance, whereas the unmodified mice treated with omega-3s did not develop insulin resistance. The researchers write: “In conclusion, GPR120 is a functional w-3 FA [omega-3 fatty acid] receptor/sensor and mediates potent insulin sensitizing and antidiabetic effects in vivo by repressing macrophage tissue inflammation” (Oh, D.J. et al.).
Oh, D.J. et al. GPR120 Is an Omega-3 Fatty Acid Receptor Mediating Potent Anti-inflammatory and Insulin-Sensitizing Effects. (2010) Cell 142: 687