Critical role of habenula lateral circuits in controlling stress-induced palatable food consumption Summary Chronic stress fuels the consumption of palatable foods and can increase the development of obesity. Although stress and feeding control pathways have been identified, how stress-induced eating is orchestrated remains unknown. Here, we identify Npy1r-expressing neurons of the lateral habenula (LHb) as the critical node for promoting hedonic eating under stress, as the lack of Npy1r in these neurons alleviates the obessive effects caused by stress combined with high-protein feeding. fats (HFDS) in mice. Mechanistically, this is due to a circuit originating in central amygdala NPY neurons , with HFDS-induced NPY upregulation initiating a dual inhibitory effect via Npy1r signaling in LHb and lateral hypothalamus neurons. , thus reducing the homeostatic satiety effect through action on the ventral downstream of the tegmental area. Together, these results identify LHb-Npy1r neurons as a critical node for adapting the chronic stress response by driving palatable food intake in an attempt to overcome the negative valence of stress. |
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When you’re stressed, a high-calorie snack may seem like a comforting option. But this combination has an unhealthy drawback. According to Sydney scientists, stress combined with high-calorie "comfort" food creates changes in the brain that drive you to eat more, increase cravings for sweet and very tasty foods and lead to excessive weight gain.
A team at the Garvan Institute of Medical Research found that stress overrode the brain’s natural response to satiety , generating continuous reward signals that promote the consumption of tastier foods. This occurred in a part of the brain called the lateral habenula , which when activated generally dampens these reward signals.
"Our findings reveal that stress can override a natural brain response that decreases the pleasure gained from eating, meaning that the brain is continually rewarded for eating," says Professor Herzog, lead author of the study and visiting scientist at the Garvan Institute. .
"We show that chronic stress, combined with a high-calorie diet, can lead to increased food intake as well as a preference for sweet and highly palatable foods, promoting weight gain and obesity. This research highlights how crucial a healthy diet is in times of stress."
The research was published in the journal Neuron .
From stressed brain to weight gain
While some people eat less during times of stress, most will eat more than usual and choose high-calorie options high in sugar and fat. To understand what drives these eating habits, the team investigated in mouse models how different areas of the brain responded to chronic stress under various diets.
"We found that an area known as the lateral habenula , which is normally involved in turning off the brain’s reward response, was active in mice on a short-term high-fat diet to protect the animal from overeating. However, when the mice were chronically stressed, this part of the brain remained silent , allowing reward signals to remain active and encourage pleasurable eating, without further responding to satiety regulatory signals," explains first author Dr. Kenny Chi Kin Ip, Garvan Institute.
"We found that mice stressed on a high-fat diet gained twice as much weight as mice on the same diet that were not stressed."
The researchers found that at the center of the weight gain was the molecule NPY, which the brain naturally produces in response to stress. When the researchers blocked NPY from activating brain cells in the lateral habenula in mice stressed on a high-fat diet, the mice consumed fewer comfort foods, resulting in less weight gain.
Next, the researchers performed a ’sucralose preference test’ , allowing the mice to choose to drink water or artificially sweetened water.
"Mice stressed on a high-fat diet consumed three times more sucralose than mice on a high-fat diet alone, suggesting that stress not only triggers greater reward from eating, but also specifically generates a craving for sweet and tasty foods," says the professor. Herzog. "Crucially, we did not see this preference for sweetened water in stressed mice on a regular diet."
Stress overrides healthy energy balance
"In stressful situations, it’s easy to use up a lot of energy and the feeling of reward can calm you down; this is when a boost of energy through food is helpful. But when experienced over long periods of time, stress seems to change the equation, driving eating that is bad for the body in the long term," says Professor Herzog.
The researchers say their findings identify stress as a critical regulator of eating habits that can override the brain’s natural ability to balance energy needs.
"This research emphasizes how much stress can compromise a healthy energy metabolism," says Professor Herzog. "It’s a reminder to avoid a stressful lifestyle and, more importantly, if you’re dealing with long-term stress, try to eat a healthy diet and cut out junk food."
