Fatty diet leads to fat-loving brain cells

Cheeseburgers pack on the pounds, but in mice a high-fat diet also packs on new nerve cells in the brain. More brain cells may seem like a good thing, but these newly sprouted cells appear to trigger weight gain in the animals, a new study finds.

The results offer insight into how the brain controls weight. If the same thing happens in humans, these nerve cells may be a target for anti-obesity treatments.

“This kind of work will definitely inform how we think about the underlying factors that relate to obesity,” says endocrinologist Jeffrey Flier of Harvard Medical School in Boston. There’s increasing interest, he says, in how long-term changes in brain circuitry — like new nerve cell production — affect eating and hunger. “That is going to be a very interesting frontier.”

With some key exceptions, most regions in the adult brain don’t make new nerve cells. But in a small sliver of brain tissue called the median eminence, new nerve cells are born throughout life, neuroscientist Seth Blackshaw of Johns Hopkins University School of Medicine and colleagues report online March 25 in Nature Neuroscience. The median eminence is part of the brain’s metabolism hub known as the hypothalamus.

And one signal to step up production in the median eminence, the team found, is a diet high in fat.

In the study, mice that ate the rodent version of a steady stream of Big Macs gained weight. This unhealthy diet also kicked nerve cell production into high gear, the scientists found. After eating a fatty diet for several weeks, adult mice pumped out about four times as many new nerve cells in the median eminence as mice that ate regular chow.

To see whether these newborn nerve cells were up to no good, Blackshaw and his team shut down production with a carefully targeted laser. Even while continuing to gorge on a high-fat diet, these mice started moving around more and didn’t gain as much weight as mice on a high-fat diet that could still make the new nerve cells. Take away the steady stream of new nerve cells, and the pounds didn’t pile on as fast.

The newborn cells’ parents turn out to be a mysterious kind of brain cell that resides in the median eminence. Both mice and people have these cells, called tanycytes, but no one knew what their role was. “There’s been a lot of speculation about what their function may be,” says Blackshaw.

The scientists don’t yet know how these newborn nerve cells can influence metabolism. Other studies, including those by Flier, have found that a high-fat diet actually reduces nerve cell turnover in other parts of the hypothalamus.

Blackshaw cautions that it’s too soon to say whether a similar thing could be going on in people. “This is the very first step in trying to understand this process,” he says. “We’re a long way from realizing whether this is relevant to human obesity.”