Researchers led by Andrew Dillin, a professor of molecular and cell biology at the University of California, Berkeley, were surprised to discover that mice lacking a sense of smell do not gain weight, despite being fed a high-fat diet.
The results of the new study were published in the journal Cell Metabolism, and the findings point to an unexplored link between olfactory neurons and weight gain.
As the authors of the research explain, it is known that our sense of smell, together with the olfactory input from the environment, help us to select and appreciate food. The sense of smell and that of taste are heightened before a meal, and they tend to decline immediately afterward.
But the physiologic role of the sense of smell, as well as exactly how it contributes to overall energy balance, is not fully understood.
To find out more about this, Prof. Dillin and colleagues created a mouse model wherein the rodents were genetically engineered to lack olfactory receptor neurons, which are the cells that line the nasal cavity, responsible for sending the olfactory information to the brain.
They also looked at the “energy homeostasis” of the mice – that is, the balance between food consumption and energy expenditure.
Studying mice that cannot smell
The most intuitive explanation for why mice without a sense of smell might not gain weight would be that they do not eat as much. But Prof. Dillin and colleagues compared the food intake of mice without a sense of smell with that of control mice, only to find that the mice that had their sense altered ate just as much as those in the control group.
Additionally, the team accounted for potential differences in how well the nutrients were absorbed and excreted. The researchers also examined the effect of mice losing their olfactory sense after they became obese.
For example, two mice that had both been fed the same high-fat diet became obese, with only one of the mice then having their sense of smell switched off. This mouse’s weight decreased by approximately a third, reaching a weight of 33 grams. By contrast, the mouse that retained its sense of smell also retained its weight of 49 grams.
Prof. Dillin and team went on to investigate whether they could replicate their findings in a second mouse model. In this model, the researchers used a virus that killed olfactory neurons when inhaled.
This procedure was thought to be more precise than the one used in the first mouse model, as the researchers feared that the drug used the first time around would annihilate more than just the olfactory sensory neurons.
The second mouse model revealed very similar results.
Fat burning mechanism activated
Prof. Dillin and colleagues also set out to investigate the role of the sense of smell on energy expenditure. Namely, they looked at the link between white fat, brown fat, and disruption of the olfactory sense.
The researchers found “increased energy expenditure and enhanced fat burning capacity as a consequence of enhanced sympathetic nerve activity.”
The sympathetic nerve system normally helps the body to control its “fight-or-flight” response to situations perceived as dangerous, as well as its response to extreme temperatures.
In such extreme situations, the body releases adrenaline. And as Prof. Dillin explains, adrenaline is known to activate the “brown-fat-burning program.”
The researchers believe that the absence of a sense of smell boosted the activity of the sympathetic nervous system; they found high levels of adrenaline in the rodents’ blood.
The mice without a sense of smell were found to burn their brown fat quicker and turn the white fat into brown. “The mice with no sense of smell had turned on a program to burn fat,” as Prof. Dillin puts it.
White fat and brown fat fulfill different functions: white fat stores energy, while brown fat expends it. In previous studies, turning white fat into brown has been associated with a lower body mass index (BMI) and has been proposed as a good strategy in the fight against obesity.
So what do the new findings mean for us? The researchers say that if their results can be replicated in human trials, new treatments for people with eating disorders may be in the cards.
“People with eating disorders sometimes have a hard time controlling how much food they are eating and they have a lot of cravings,” says study co-author Céline Riera, of Cedars-Sinai Medical Center in Los Angeles, CA.
“We think olfactory neurons are very important for controlling 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.”
Next, the researchers plan to examine which neural pathway is responsible for the connection between the olfactory neurons and the sympathetic nervous system.