#CAN2014 (So long and) thank you for all the fish: on omega-3s and GRP120
(Notes from the 2014 Canadian Association for Neuroscience annual meeting in Montreal, Canada. Title credit: The hitchhiker's guide to the galaxy.)
Nutritional science is seriously confusing, but generally people agree that omega-3 fatty acids are good for you. Most often found in fatty fishes, edamame and flax, omega-3s reduce inflammation and lower blood triglycerides levels, which may protect against stroke and heart attacks. Incredibly, dietary omega-3s that travel our alimentary canals can find their way into the brain, where they promote satiety and reduce anxiety – at least in rodents. How fish oil tweaks brain activity is a mystery.
Once ingested, omega-3s act like drug molecules, seeking out and binding to their protein receptors in the body. One such receptor, GRP120, is particularly important as it stimulates anti-inflammatory effects and also enhances insulin sensitivity in mice. When GRP120 signalling goes wrong, both mice and humans tend to develop obesity. Since GPR120 is also found in the brain, a team of neuroscientists from the University of Montreal decided to see if this receptor also mediates omega-3’s brainy effects.
The team injected a chemical that selectively activates GRP120 directly into the brains of mice, and then placed the animals into specialized chambers to monitor their metabolism. Activating GFP120 seemed to make mice more jittery: for roughly an hour after injection, the mice constantly scuttled around their chambers while rejecting freely-available chow. Although they quieted down after an hour, the animals still flatly refused to eat for at least 4 hours after GRP120 activation. At the same time, scientists found a decrease in their respiratory exchange ratio, which indicates that their bodies are preferentially burning fat as a fuel source instead of carbohydrates – probably due to the lack of food intake. Stimulating GRP40, a similar fatty acid receptor did not inhibit feeding. Unlike GRP120, GRP40 primarily responds to medium-chain fatty acids such as palmitic acid (a saturated fatty acid) and linoleic acid (an omega-6 fatty acid).
Next, the team tried to tempt these mice with decadent food pellets loaded with sugar and fat. But there was a catch: the mice had to press a lever for the pellets, and as the trial went on, more presses were needed to get the same amount of food reward. This test is often used to gauge an animal’s motivation. GRP120 activation caused mice to give up sooner and with less total food reward than their saline-injected peers. This suggests that the activated GRP120 reduces the motivation to work for food. It could also mean that GRP120 stimulation directly increases satiety, so that the animals didn’t feel the need for more dessert. In a separate test assessing the animal's anxiety levels, stimulating GRP120 made them chill out somewhat, but the effect sizes were too small to be definitive.
These preliminary data suggest that omega-3s can help reduce food intake by acting through GRP120 in the brain. But keep in mind that the study didn't directly use omega-3s for injection, and that dietary omega-3s may not reach the brain in sufficient amounts to trigger the same effect. As of now, the evidence for omega-3s as weight-loss supplements in humans is very limited and controversial, so don’t go guzzling that fish oil yet.
Poster 2-F-146: Central GPR120 activation inhibits food intake, food reward and anxiety-like behavior. Stéphanie Auguste, Maria Fernandes, Vincent Poitout, Thierry Alquier, Stephanie Fulton. University of Montreal.