Lighten up. Mice with fatty acid binding proteins (right) gained more weight on a high-fat diet and had worse metabolic function than their counterparts without the proteins.

Haiming Cao/Harvard School of Public Health

Fat Molecule Fights Weight Gain

It could be an ad in a fashion magazine: Miracle fat prevents weight-gain! Researchers aren't promising that, but they do say they've isolated a fat molecule in mice that prevents the animals from storing even more fat. The discovery could open a new front in the battle against the bulge if the molecule has the same effect in humans.

The word "fat" typically evokes the image of clogged arteries or cellulite jiggling on a thigh. But fat has a good side, too. Fat cells make up adipose tissue, which helps regulate insulin levels and breaks down dietary fat for energy. This breakdown is accomplished via proteins in fat cells called fatty acid–binding proteins. Mice genetically engineered to lack these proteins gain less weight and are less susceptible to metabolic diseases such as diabetes than are regular mice.

Biochemist Gökhan Hotamisligil of the Harvard School of Public Health in Boston and his colleagues wanted to understand how this process works. They set up an experiment to compare normal mice that produce the binding proteins with mice engineered to lack them. Half the mice in each group ate a high-fat diet for 16 weeks while their counterparts crunched on low-cal food. At the end of the treatment, the researchers tested how much and what types of fat built up in adipose tissue, blood, liver, and muscle. They also tested metabolic function in mice. They saw that mice on the high-fat diet without fatty acid–binding proteins did gain weight but less weight than the control mice on the high-fat diet. Most surprisingly, the mice without binding proteins had better metabolic function and more of the fat that's considered healthy than the controls, the team reports today in Cell.

The researchers then examined why the mice were accumulating less fat, suspecting that a molecular signal was in play. "It was like looking for a needle in a bad, gooey, sticky, nasty haystack," says Hotamisligil. Upon further investigation, the team found elevated levels of one type of fatty acid, palmitoleate, in adipose tissue of the genetically engineered mice. Palmitoleate is formed when cells produce their own fat, even good fat, and Hotamisligil suspects that the molecule sends a signal to other organs in the body telling them not to store extra dietary fat. He now wants to see if this "healthy fat" has the same effect in humans.

The idea that a fatty acid could help regulate the metabolic system is fascinating and provocative because researchers had thought only proteins could do that, says Henry Ginsberg, an endocrinologist at Columbia University. "Definitely, a lot of people should be looking at this."