Mice shed weight when they can’t smell—but not because they stop eating

When you have a stuffy nose, a slice of freshly baked apple pie tastes like mush. But not being able to smell your food could have a surprising effect on your metabolism, potentially helping you remain thin even when you eat fatty foods, a new study in mice suggests.

“This is a very exciting study, and the outcome is quite compelling,” says neuroendocrinologist Tamas Horvath of Yale School of Medicine, who wasn’t connected to the research.

To conduct the study, molecular biologist Andrew Dillin of the University of California, Berkeley, and colleagues turned to a variety of genetically altered mice. The scientists gave them regular doses of the diphtheria toxin—which causes a temporary loss of odor-sensing neurons—to suppress their sense of smell. They then fed the rodents either a normal diet or fatty foods—the mouse equivalent of cheesecake and pizza—that usually induce obesity.

After more than 3 months of noshing on regular chow, the odor-deprived rodents weighed slightly less than mice whose sense of smell was intact. In the group on the high-fat diet, however, the mice that couldn’t smell weighed 16% less than animals that could, which became obese. Losing the ability to smell also caused a different group of already-obese mice to lose weight, the researchers reveal today in Cell Metabolism.

The obvious explanation for this effect—that mice with impaired olfaction were eating less—turned out to be wrong. There was no difference in the animals’ food consumption. Nor were the slim rodents getting more exercise. They weren’t moving around their cages more than their porky counterparts.

Instead, the researchers determined, they stayed svelte because they burned more calories, especially in their brown fat. Unlike the white fat that accumulates on our bellies and thighs, brown fat is specialized to produce heat through metabolism. Adult humans have only a small amount of brown fat, but rodents carry plenty of it, and it’s crucial for maintaining their body temperature. Dillin and colleagues found that not only did the brown fat ramp up its activity in the smell-deficient animals, but some of their white fat also became more like brown fat. “They rewire their metabolic programming to burn more calories,” he says. When a mouse can’t smell its food, he speculates, it may “think” that it has eaten more than it really has, prompting it to use more energy.

Dillin and his colleagues next asked what happened if the animals’ sense of smell were sharper. The researchers followed weight changes in a different group of genetically engineered rodents that are hypersensitive to odors. These super-smellers became obese, but not because they consumed more food than usual. That result supports the idea that the sense of smell modifies how much energy the animals use. “There’s more to gaining weight than just eating food—it’s how you are perceiving the food,” Dillin says.

“The idea that smell is directly involved in energy balance is surprising,” says neuroanatomist Laurent Gautron of the University of Texas Southwestern Medical Center in Dallas. Electrophysiologist Debra Fadool of Florida State University in Tallahassee agrees that the result is intriguing, describing the work as “important and timely.”

Whether humans respond in the same way to losing their sense of smell isn’t clear, cautions clinical neuroscientist Thomas Hummel of the Technical University of Dresden in Germany. He and his colleagues have studied people who could no longer detect odors because of head injuries or other causes. Few lost weight, he notes. But if researchers do demonstrate the effect in humans, temporarily suppressing the sense of smell could provide a new way to fight obesity. For instance, Horvath suggests, it might be possible to develop a nasal spray that would deaden the odor-sensitive neurons for a few hours. People could spritz a dose before they eat to help keep their weight under control.