Without a sense of smell, fat burns away

A mouse with no sense of smell won’t gain as much weight as another rodent fed the same high-fat diet; conversely, a rat with a super-sense of smell will put on more weight.

“It’s one of the most interesting discoveries to come out of my lab,” says Andrew Dillin, professor of molecular and cell biology at the University of California, Berkeley, of the research he and colleagues have just published in the journal Cell Metabolism.

The results may have profound implications for medical research on weight gain and loss. They also point to the complex interrelationships of physiological systems and show how emerging techniques designed to target specific conditions by switching particular proteins, genes or cells on or off may have unintended consequences.

In this case, the researchers from UC Berkeley, the Salk Institute for Biological Sciences, also in California, and the Max Planck Institute for Metabolism Research in Germany tested for a possible relationship between sense of smell (“olfactory perception”) and fat-burning capability (“energy homeostasis”) in both lean and obese mice by temporarily destroying their olfactory sensory nerves.

This was done using two techniques. The first involved mice genetically engineered with a diphtheria receptor in their olfactory neurons. To check that the chance the genetic tinkering was not affecting more than just olfactory sensory neurons, a second technique involved an inhaled virus that similarly killed off the mice’s olfactory sensory neurons when a diphtheria toxin was sprayed into their noses.

The result: the mice were resistant to diet-induced obesity, demonstrating increased burning of brown fat with the body’s other form of fat, white fat, being transformed into brown fat. While control mice doubled their weight on the high-fat diet they were fed, the weight of the mice with no sense of smell increased by just 10%. The test mice that were already obese lost only fat weight, with no effect on muscle, organ or bone mass. “Acute loss of smell perception after obesity onset not only abrogated further weight gain but also improved fat mass and insulin resistance,” the researchers report.

Conversely, tests with a strain of mice that are mice that are supersmellers, developed by researchers at the Max Planck Institute, showed they gained more weight on a standard diet than did normal mice.

Lead author Céline Riera says this is one of the first studies to really show the relationship between the sense of smell and how the brain perceives and regulates energy balance. “People with eating disorders sometimes have a hard time controlling how much food they are eating and they have a lot of cravings,” she says. “We think olfactory neurons are very important for controlling the pleasure of food and if we have a way to modulate this pathway, we might be able to block cravings in these people and help them with managing their food intake.”

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