Steven Munger, Ph.D.

A number of recent press articles have reported on the publication of a research paper which suggests that mice with hyposmia (a reduced sense of smell) are resistant to diet-induced obesity.  But is this fact, fiction, or somewhere in between?  We wanted to get an expert’s perspective, so we spoke to Dr Steven Munger, Director of the University of Florida Center for Smell and Taste, who kindly penned the following article.

Does smell loss protect against obesity?

A central role for the senses of smell and taste is to help us make decisions about food. Should we eat it or throw it away? Do we like it, or find it disgusting? People with smell or taste impairments miss out on some (or all) of the information that odors and tastes convey about food and drink.

But a recent scientific study has prompted the question: do chemosensory disorders have any positive health impact? A new study published in the journal Cell Metabolism reports that mice with hyposmia (reduced smell) are resistant to diet-induced obesity. Perhaps unsurprisingly, many websites and media reports have chosen more provocative headlines suggesting that the sense of smell makes you fat, or that inhibiting your sense of smell could help you stay thin. But this is a dangerous leap.

The scientists who performed this study set out to understand the relationship between olfaction and metabolism. Given the relevance of smell to food choice and assessment, this was a great issue to investigate.

To test the impact of reduced smell on metabolism and weight gain, the researchers used a number of techniques to destroy many (but not all) of the mice’s olfactory sensory neurons (or “OSNs”)* within the olfactory epithelium – a layer of tissue at the top of the nasal cavity that is specialized for detecting odors. They found that when fed a high fat diet, mice in which the OSNs had been selectively destroyed gained less weight and burned more energy than did mice with an undamaged olfactory epithelium (there was no difference between the two groups maintained on a normal diet). This was the case even though the mice with fewer OSNs ate the same amount of food as the “normal” mice.

But are these changes in weight and metabolism a result of a reduced ability to smell? And if so, what is the relevance for humans? Some key questions, and cautions, remain. These include:

• Were the changes due to smell loss, or to some other damage that accompanied the OSN destruction? Perhaps the most significant question is whether the effects on metabolism and weight gain are actually due to a decreased ability to smell. The researchers chose to impair the mice’s sense of smell by destroying some of the OSNs in the olfactory epithelium. It’s possible that the epithelium normally produces a hormonal or neural signal that impacts metabolism. Indeed, many organs in our bodies serve multiple functions that are loosely related but separate. Therefore, the metabolic changes seen in these mice may not be due to the loss of smell, but to the removal of some other olfactory epithelium function. Future studies could clarify this possibility by examining if the same metabolic changes are seen in animals with reduced or absent sense of smell but with an otherwise intact olfactory epithelium. Several types of genetically-engineered mice exist that could be used in such experiments.

• Are these mice hyposmic? Disappointingly, only very rudimentary olfactory testing was used in a study focused on the impact of smell. The “buried food test”, which measures the time it takes for a mouse to find a buried food pellet, was the principal test employed to assess olfactory ability in these mice. While this assay may be a useful first test of olfaction, it does a poor job of measuring the severity of the deficit. Other factors can affect the results of this test, as well: the mouse may be less motivated, or less active. Much more specific behavioural and physiological tests can be used to confirm and quantify any loss of smell.

• Does age or experience play a role? In this study, OSNs were destroyed in adult mice that had been born with a normal olfactory system. So, this was a model of “acquired hyposmia.” Did the animals’ previous experience with odors impact the results? Would body weight and metabolic parameters return to “normal” if the animals were tested many months after the olfactory damage first occurred? What was the impact of the relatively limited odor environment and single food choice for these laboratory mice? These are just some of the questions that will need to be addressed in future studies.

• Mice are not humans. Mice have been, and continue to be, invaluable research models for understanding human physiology and disease. This is certainly true in the study of olfaction, and even of smell disorders. However, there are significant differences between mouse and man, from our genes and proteins to our social environment and cognitive abilities. Research investigating the impact of smell impairment on eating, obesity and/or metabolism in humans is remarkably rare. This study serves to highlight the need for more studies of the effects of smell impairment in humans in addition to the ongoing research in mice and other model systems.

The key message here is that we are a long way from linking anosmia or hyposmia to protection from either obesity or metabolic change. One hopes that no one would try to purposefully damage their olfactory system in pursuit of weight loss. As many people affected by olfactory disorders know only too well, the wide-ranging consequences of smell loss are not to be taken lightly.

* The OSNs are specialized cells that receive odor signals and transmit this information to the brain. OSNs are found in a tissue at the top of nasal cavity called the olfactory epithelium. In many cases of anosmia or hyposmia, it is the OSNs that are damaged or missing (though other causes include damage to olfactory brain areas and blockage of nasal passages).

For more information on the University of Florida Center for Smell and Taste visit http://cst.ufl.edu