First lipid hormone discovered

Fatty acid helps boost insulin action and protects against fat buildup in the liver.

Some fats are just better than others. Omega-3 fatty acids, such as the fats that compose fish oil, have been recognized for their health-promoting benefits.

Well, move over, omega-3s; now there’s a fat that’s even phatter. Researchers at HarvardUniversity and Lipomics Technologies in West Sacramento, Calif., have discovered that a fatty acid can make mice super healthy.

An omega-7 fatty acid called C16:1n7-palmitoleate works as a health-promoting hormone, the researchers report September 19 in Cell . Palmitoleate is made by fat and liver cells, the team discovered. The lipid, or fatty acid, signals muscles to respond to insulin, prevents the harmful buildup of fats in the liver and reduces levels of inflammatory chemicals made in fat cells.

The new study “really suggests that lipids, fatty acids, could have a signaling effect,” says Clay Semenkovich, an endocrinologist at WashingtonUniversity in St. Louis. “This is something people have postulated for a while, but has been difficult to get a handle on.”

Palmitoleate is the first lipid demonstrated to work as a hormone, a job usually done by proteins, such as insulin, or by small molecules, such as adrenaline. If the lipid works the same way in people as it does in mice, the fatty acid some day could be added to foods or given as a supplement to improve human health and ward off heart disease and diabetes.

Researchers led by Gökhan Hotamisligil, a geneticist at Harvard, had previously created extraordinarily healthy mice by preventing the mice from making two proteins that normally bind to fatty acids. Previous research had shown that blocking the action of the proteins could improve health, but the mice lacking both proteins had health “beyond the normal range,” Hotamisligil says. “Almost indestructible. No heart disease, fatty liver disease, diabetes, no asthma, nothing.” And their excellent health held up even when the mice ate a high-fat diet.

But the reason the mice were so healthy wasn’t apparent. “The general dogma in the field is the more fatty acids you have in the blood, the sicker you are,” Hotamisligil says. But the mutant mice had slightly higher levels of fatty acids in their blood than normal mice do.

Endocrinologists have learned that “Fats are not just fats,” Semenkovich says. “You can have the same level of circulating fatty acids in two people, but if the composition is different, it could have very different health outcomes.”

When the scientists examined which fats were present in the über-healthy mice, they found that palmitoleate, a normally rare lipid, was the third most abundant fatty acid in the healthy mice’s blood. The lipid improves muscle responses to insulin and prevents liver cells from accumulating other harmful fats, the researchers found. Palmitoleate also reduces the amount of inflammation-promoting chemicals produced by fat cells. Inflammation has been linked to heart disease, diabetes and other illnesses.

Because the mice were missing the two proteins, their fat cells were not able to store fat from the mice diets. The fat cells instead made their own fat, primarily palmitoleate.

Liver cells also make the lipid hormone, the researchers found. In normal mice, the lipid is produced at low levels. When the mice eat a high-fat diet, their cells cut palmitoleate production in half. But the super-healthy mice continue making lots of the lipid, even when they eat diets rich in fat.

People probably also respond to fat-filled diets by reducing palmitoleate production, Hotamisligil says. “A caveman chasing a deer probably had active production of this material, but not us constantly stuffing ourselves with calories.”

Rather than supplementing the diet with palmitoleate, Hotamisligil thinks it would be healthier to persuade people’s own fat cells to produce more of the lipid. “What you make yourself is always the best,” he says. “It’s like homemade cooking.”

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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