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Decreasing body weight via temporary ablation of the sense of smell

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Shubhankar Kulkarni
Shubhankar Kulkarni Aug 19, 2020
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A large number of strategies are being used and developed for weight loss. A study measured the effect of ablating the mature olfactory sensory neurons in adult mice on energy homeostasis. These hyposmic (reduced ability to smell) mice exhibited normal food intake and body weight on a regular diet, but were resistant to obesity caused by a high-fat diet. The authors found out that this resistance was due to both reduced high-fat food intake and increased energy expenditure. They also found improved fat mass and reduction in insulin resistance in these mice. It was demonstrated that this increased energy expenditure was due to an increase in the activity of the brown adipose tissue. Sympathetic nerve activity and β-adrenergic receptors on white and brown adipocytes were stimulated to promote lipolysis. The authors generated mice with enhanced smelling ability by ablating the insulin-like growth factor 1 receptor on the olfactory sensory neurons. These mice exhibited increased body weight without any changes in food intake. Thus, the olfactory system can regulate body weight via changes in energy expenditure.

There definitely are differences between the olfactory system of mice and humans. However, temporary ablation or desensitization of the olfactory sensory neurons seems like a promising strategy to decrease body weight in humans.

[1]Riera CE, Tsaousidou E, Halloran J, Follett P, Hahn O, Pereira MMA, et al. The Sense of Smell Impacts Metabolic Health and Obesity. Cell Metab [Internet]. 2017 Jul;26(1):198-211.e5. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1550413117303571

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General comments

Povilas S
Povilas S3 years ago
There would most likely be side problems caused by decreased sense of smell. This very example of recent discovery that olfaction is related to body weight regulation shows that many other important connections between this perception and other bodily functions might not yet be explored and understood. Olfaction is closely linked with memory and emotions and its reduction might affect those mental aspects. Smells also most likely have a significant influence on our subconscious. So the consequences of reduced sense of smell for a longer time might not be that harmless. Of course, for people with serious obesity problems trying it would probably be worth the risk.
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Shubhankar Kulkarni
Shubhankar Kulkarni3 years ago
Povilas S Exactly, this is not for someone looking to shed a few pounds. It is for those obese people who require gastric bypass and other surgeries in order to reduce body weight. Moreover, what I suggest is non-invasive. A targeted drug can probably deactivate the olfactory neurons. What I am thinking of is taking a pill once a day and wait (to have food) till its effects wear off. This will essentially decrease the food intake (which is what gastric surgeries do). Another technique is to use magnetic fields to deactivate neurons temporarily (ncbi.nlm.nih.gov/pmc/articles/PMC3063755/). I don't know whether this can be targeted solely towards the olfactory neurons.
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Subash Chapagain
Subash Chapagain4 years ago
Given the ever-increasing figures of obesity and related disorders all across the world, such a novel approach to lower the body weight indeed would be highly useful. It is true that when something smells 'so good', we are always tempted to 'taste' it even if we are not nutritionally deficient. Everything after that is a slippery slope, given the dopamine reward system that we are so poor at inhibiting. Hence, a biological solution like olfactory ablation would be hugely beneficial, if it could be developed effectively. However, there are some critically important issues we need to address before considering applying this kind of desensitization to humans. Here are a few: 1. What exact sensory mechanisms are we targeting to inhibit the sense of smell? How do we plan to do it? Will it be transient or a long-lasting one? 2. Olfactory reception is one of the most complex biological sensing machinery ever to exist; hence, while ablating the sense of smell, how can we be specific enough to exactly pinpoint which biomolecules (mainly transmembrane proteins) to target? 3. Olfactory Receptors (OR) family of genes is one of the largest multigene family known to the mammalian system. The fact in itself is sufficient for a healthy dose of skepticism to think very critically before deciding to shut the whole system down just to meet one target of reducing the body weight. Most of the genes involved in these signalling pathways are homologous across other systems as well. For example, some of the receptors involved in sensing of smell are G-protein Coupled Receptor (GPCR) family of protein which also is the family of proteins like Rhodopsin that are involved in light sensing and visual perception. Hence, to guarantee that all kinds of cross-silencing are avoided, what molecular tools do we need to develop first? 4. The olfactory system is responsible not only for the food-related sensory signalling but also has a lot of social and behavioural implications. We know that sense of smell is very important evolutionarily when it comes to determining cues about possible partner for mating, and also for mother-child bonding. Hence, while we go on to ablate the sense of smell, can we guarantee that we will have no negative impact on these evolutionary and behavioural uses of the system? 5. How do we determine the selectivity of silencing? There are good smells that make us want to eat more, but also there are pungent smells that let us know of potential toxicity and obnoxious environment. Given that there is an infinite range of molecular combination out in the environment and hence an infinite number of smells that we might encounter, how do we target which smell to allow and which not to? If we can answer these questions with an approximated confidence, then this solution would be one of the best that exists when it comes to body-weight loss and the fight against obesity relate diseases. References: 1. Niimura Y. Evolutionary dynamics of olfactory receptor genes in chordates: interaction between environments and genomic contents. Hum Genomics. 2009;4(2):107-118. doi:10.1186/1479-7364-4-2-107 2. Sarafoleanu C, Mella C, Georgescu M, Perederco C. The importance of the olfactory sense in the human behavior and evolution. J Med Life. 2009;2(2):196-198. 3. Julius D, Nathans J. Signaling by sensory receptors. Cold Spring Harb Perspect Biol. 2012;4(1):a005991. Published 2012 Jan 1. doi:10.1101/cshperspect.a005991
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