A high-fat diet without the weight gain? Study says it's possible

When it comes to gaining weight, a high-fat diet is a key culprit. New research, however, suggests that there may one day be a way to avoid piling on the pounds as a result of eating fatty foods.

Researchers were able to prevent weight gain in mice fed a high-fat diet.

In a newly published study, researchers reveal how activating a specific protein pathway can prevent the growth of fat cells in mice in response to a high-fat diet.

Senior study investigator Fanxin Long, Ph.D. — who works in the Washington University School of Medicine in St. Louis, MO — and colleagues say that their findings could bring us closer to a new treatment strategy for obesity, which is, at present, thought to affect more than a third of adults in the United States.

The researchers recently reported their results in the journal eLife.

Weight gain is most commonly caused by an energy imbalance, wherein the intake of calories is higher than the number of calories burned.

Over time, an energy imbalance causes the body to store fat. This can lead to weight gain and obesity — which is a risk factor for type 2 diabetes, heart disease, stroke, and some types of cancer.

Foods high in fat, particularly saturated fats, are thought to be a main driver of obesity, especially when consumed in large amounts. But Long and colleagues suggest that there could be a way to prevent weight gain induced by a high-fat diet.

Hedgehog signaling and fat cells

For their study, the team focused on the Hedgehog signaling pathway, which is a complex network of proteins that play a role in various developmental processes.

Previous research in mouse models has shown that the Hedgehog signaling pathway can also inhibit adipogenesis, or the formation of fat cells.

According to Long and his team, the majority of studies have looked at the effects of Hedgehog signaling on adipogenesis during embryonic development, so it has been unclear as to whether activating this pathway in adulthood influences fat cell formation.

To find out, the researchers engineered adult mice to possess genes that activated the Hedgehog signaling in response to a high-fat diet. These rodents were fed a high-fat diet for a total of 8 weeks.

While a control group of mice — whose Hedgehog signaling pathways were not activated when they ate fatty foods — became obese after 8 weeks of a high-fat diet, the genetically engineered mice gained no more weight than control mice that consumed standard chow.

"More importantly," notes Long, "when we did metabolic studies, we found that the animals with the active Hedgehog pathway not only were leaner, they also had lower blood glucose levels and were more sensitive to insulin."

A new way to fight obesity?

The researchers explain that by activating the Hedgehog signaling pathway in the rodents upon consumption of a high-fat diet, they were able to reduce the size of fat cells.

"Fat gain is due mainly to increased fat cell size," explains Long. "Each fat cell grows bigger so that it can hold larger fat droplets. We gain weight mainly because fat cells get bigger, as opposed to having more fat cells."

But the researchers note that applying their results to humans will be challenging; heightened Hedgehog signaling has been linked to increased cancer risk, so any strategy that targets this pathway would need to be approached with caution.

That said, the team believes that its results show promise for a new approach to preventing weight gain.

"If we can come up with strategies to carefully target fat cells, then I think activating this pathway could be effective in the fight against obesity."
Fanxin Long, Ph.D.

"What's particularly important," Long adds, "is that the animals in our study ate a high-fat diet but didn't gain weight, and in people, too much fat in the diet is a common cause of obesity."

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