A mouse smelling its food [JanPietruszka / 92906697 / iStock / Getty Images Plus]
Scientists at the Max Planck Institute for Metabolism Research have identified a network of nerve cells that may be responsible for a reduction in feelings of hunger that may be felt as a result of smelling food, in mice. The team discovered a direct connection from the nose to a group of nerve cells in the brain that are activated by the smell of food and, when activated, trigger a feeling of fullness in lean mice, but not in obese mice. The discovery may suggest that treating obesity might require different advice about smelling food before a meal based on a person’s weight.
“Our findings highlight how crucial it is to consider the sense of smell in appetite regulation and in the development of obesity,” said study lead Sophie Steculorum, PhD, research group leader at the Max Planck Institute for Metabolism Research. “Our study shows how much our daily-lives’ eating habits are influenced by the smell of food. Since we discovered that the pathway only reduces appetite in lean mice, but not in obese mice, our study opens up a new way to help prevent overeating in obesity.”
Steculorum and colleagues reported on their findings in Nature Metabolism, in a paper titled “A food-sensitive olfactory circuit drives anticipatory satiety.” In their report, the authors stated, “Here, we uncover a previously unreported sensory neurocircuit that coordinately integrates food odors to regulate impending food intake, highlighting the importance of anticipatory food sensory perception in the control of satiety.”
Tight regulation of feeding behavior requires the coordinated integration of homeostatic signals aligned with the detection of environmental cues, the authors wrote. “Food sensory perception has emerged as a potent regulator of specialized feeding circuits; yet, the consequences on feeding behavior and the underlying neuronal basis remain poorly understood.” The authors noted that prior studies have shown that food–predictive cues can inhibit neurons promoting the drive to eat, and activate those decreasing it, “suggesting that sensory detection of food may trigger an anorexigenic tone.”
For their newly reported study, the team aimed to investigate “…how an organism integrates anticipatory food cues before a meal and the consequences on feeding behavior in health and obesity.” Food sensory regulation of neuronal activity is triggered by hidden food or food odors, they noted, so their study focused specifically on olfactory circuits and the contributory role of food odors.
Using brain scans to investigate which regions of the mice’s brains respond to food odors, first author Janice Bulk, PhD, and colleagues identified a new group of nerve cells in the medial septum region of the brain. “Unbiased whole-brain mapping of food odor-induced brain activity revealed a potent activation of the medial septum (MS), where food odors selectively activate MS glutamatergic neurons (MSVGLUT2).” They found that these nerve cells respond to food in two steps. When the mouse smells food, the nerve cells fire and create a sensation of fullness.
This happens within a few seconds because the nerve cells are directly connected to the olfactory bulb. “Activity dynamics of MSVGLUT2 neurons uncovered a biphasic modulation of their neuronal activity with a transient activation after detection of food odors and a long-lasting inhibition following food ingestion, independent of the caloric value and identity of the food,” the scientists explained.
The nerve cells react to different food smells, but not to other smells. When the mice started to eat, these nerve cells were then inhibited. Overall, it was found that the mice ate less when these nerve cells were active before eating. “MSVGLUT2 neurons receive direct projections from the olfactory bulb (OB) and acute optogenetic stimulation of OB→MS projections selectively before food ingestion decreased feeding in lean mice,” they noted. “We think this mechanism helps mice in the wild protect themselves from predators,” commented Bulk. “By eating for shorter periods, they reduce their chances of being caught.”
In obese mice, however, the same group of nerve cells was not activated when the mice could smell food. The team’s study found that these obese mice did not feel fuller and did not eat less overall. The authors pointed out that it is already known that obesity disrupts the olfactory system, including neuronal activity in the olfactory bulb. The sensory regulation of feeding-related neurons “is blunted in obesity,” they wrote, “… suggesting a role of their sensory regulation in the establishment or progression of obesity and associated metabolic and behavioral outcomes.”
The newly identified group of nerve cells could also be affected by obesity. The reported studies showed that “…acute OB→MS optogenetic stimulation in diet-induced obese mice failed to reduce feeding, suggesting the involvement of this pathway in calorie-rich diet-induced hyperphagia and obesity development.”
The human brain contains the same group of nerve cells as the mouse, but it is not yet known whether they also respond to food odors. Studies by other research groups have shown that smelling some specific odors before a meal can reduce people’s appetite. In contrast, other studies have shown that overweight persons eat significantly more in the same situation.
In their paper, Steculorum and colleagues concluded, “… this study reveals a sensory pathway that coordinately integrates food cues to control feeding behavior by priming satiety. The discovery of this food-sensitive olfactory feeding circuit thus reveals a regulatory principle for the central control of energy homeostasis and may pave the way to a better understanding of the aetiology of metabolic disorders associated with olfactory dysfunction, such as obesity.”
