High fat diet removes brain’s natural brake on overeating

A gut-busting diet may reprogram the brain to overeat.

Cells in their brain usually send a “stop eating” signal when we’ve had enough to eat. But after mice ate fatty foods for just two weeks, their brains’ brake on overeating quieted down. That finding may help explain the complex link between food and appetite that can become muddled when people overeat.

Researchers at the University of Washington in Seattle conducted the new work. They shared their findings June 28 in Science.

Food is essential to life. Our brains have, therefore, evolved a multitude of overlapping systems to make sure animals eat enough. Garret Stuber is a neuroscientist at the University of Washington. He and his team took aim at one brain area known to be involved in eating behaviors.

This lateral hypothalamus (Hy-poh-THAAL-ah-muss) contains many diverse cells. Stuber’s group looked at the behaviors of genes in the cells here. And in one type — glutamatergic nerve cells — big differences showed up in which genes were turned on in obese mice versus lean ones.

Earlier work by Stuber’s group had suggested that these cells act like a brake on eating. When the researchers blocked these cells from firing, mice suddenly overate. They also fattened up. But it wasn’t clear how the cells’ activity changed as the mice transitioned from slim to fat.

“Obesity doesn’t just happen overnight,” notes Stuber (who conducted some of this work while he was at the University of North Carolina in Chapel Hill). To study that gradual fattening up, his group undertook a new study.

They fed mice high-fat chow. Now and again, they’d use a fancy microscope to look at how well the animals’ glutamatergic cells’ could fire off signals.

Two weeks into this high-fat binge-out — even before the mice plumped up — the activity of these nerve cells had slowed. That cell sluggishness continued as the animals grew larger over a 12-week period. Explains Stuber, the cells’ activity was “going down as a function of a high-fat diet.”

The results suggest that the high-fat diet “is removing the brake on feeding and obesity,” says Stephanie Borgland. She’s a neuroscientist at the University of Calgary in Canada. She didn’t take part in the work, but she did comment on it in the same issue of Science.

Stuber’s group doesn’t know whether these brain cells would go back to normal if the mice stopped eating the fatty foods and slimmed down. Explains Stuber, it would be hard to keep monitoring the same cells over the months it would likely take for the mice to return to a healthy body weight.

It’s hard to say whether similar cells normally control the appetite in people. Brain-imaging tests have shown that the same brain region — the hypothalamus — plays a role when people shift between hunger and feeling full.

However, Stuber notes, obesity probably affects a much wider family of cells than those studied here. Changes, he says, are “probably happening across the brain.” But understanding those complex impacts in us might ultimately point to better strategies for limiting overeating.