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The Smell of Food Affects Metabolism in Fasting Mice

The odor prompted the animals’ fat cells to release lipids into circulation.

Turkey, mashed potatoes, stuffing, pumpkin pie and sides on a table
Shafaq Zia
Shafaq Zia

Shafaq Zia is a freelance science journalist and a graduate student in the Science Writing Program at the Massachusetts Institute of Technology. Previously, she was a reporting intern at STAT, where she covered the COVID-19 pandemic and the latest research in health technology.

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The sense of smell is particularly important to many animals, such as mice, in their search for food. But food odor does more than give these animals information about their environment: It also affects their body’s use of fats, a study published Monday (November 14) in Nature Metabolism suggests.

This work, led by Toshiyasu Sasaoka at the University of Toyama in Japan, offers new insights into the neural pathways that link smell perception to adjustments in how efficiently the body turns food into energy, known as metabolic adaptation, according to Minhong Ma, a neuroscientist at University of Pennsylvania who wasn’t involved in the study. The authors of the study did not respond to requests for an interview.

Prior research has shown a close relationship between olfactory neurons, which detect smells and convey this sensory information to our brains, and metabolism. For example, a 2017 study revealed that mice that had temporarily lost their ability to smell food lost weight, whereas mice that could smell gained weight on the same diet.

But smell perception is a complex process, and understanding the underlying mechanism that connects odor perception to the hypothalamus—the brain region that controls appetite, cravings, and metabolic signals—has been challenging. This study is among the first to systematically examine this link, says Ma in an email to The Scientist, and connect it to metabolic conditions like obesity and diabetes.

The researchers started out by dividing mice that had been fasting for 24 hours into two groups. One group was put in a cage with four tubes. One released the odor of normal chow, one released the odor of a high-fat diet, and one that of a high-sucrose diet. The fourth tube had no odor and was used as a control. The other group of mice were each put in a similar cage, but were exposed to visual stimulation of food via transparent bottles placed inside the enclosure, each containing one of the three diets, as well as an empty control bottle. 

The researchers found that seeing food had no effect on the hungry animals’ exploratory behavior, whereas mice exposed to olfactory stimulation spent the most time exploring the tube that emitted the smell of a high-fat diet. The study authors concluded that fasted mice seek out already-known food on the basis of smell, not visual information. 

From there, the scientists used the same two groups of mice to look at how food odor or visual stimulation with food affect the deployment of fats in the body during fasting. When the body is deprived of energy, fatty acids are released from adipose tissues and rapidly mobilized for use by tissues all over the body. The researchers measured the levels of these fatty acids in mice after six hours of fasting and then after 16 to 24 hours of fasting. 

They found that exposure to the odor of familiar food for 60 minutes increased the levels of fatty acids in mice that had been fasting for 24 hours, but had little effect on mice that had been fasting for 6 hours. Moreover, food odor increased the ratio of oleic fatty acids—which are considered beneficial for metabolic health and preventing type 2 diabetes—to other lipids called stearate fatty acids. 

Visual stimulation with food, on the other hand, did not affect the deployment of fats in the body during fasting. 

As obesity and type 2 diabetes are global health risks, the researchers write in their paper, their findings could lead to the development of odor-based strategies to help combat metabolic disorders.  

But rodents like mice rely heavily on their sense of smell to seek food, Ma adds, and whether the same relationship between metabolism and smell perception exists in humans, who rely more heavily on visuals, remains to be seen. Haijiang Cai, a physiologist at the University of Arizona who wasn’t involved in the study, agrees that this is a limitation. According to him, all odors are encoded in an overlapping way in the cortex, rather than in discrete areas of the brain, and the process of determining which food or, possibly, nonfood odors affect the metabolism can be challenging.

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