Stress-Induced Overeating and Weight Gain: The Role of NPY Molecule and the Brain’s Desire for Comfort Food

A connection between stress and overconsumption of food, especially calorie-dense comfort foods, leading to weight gain, has been unveiled by researchers at the Garvan Institute of Medical Research in Sydney. Their study has demonstrated that stress inhibits the brain’s natural satiety mechanism, particularly in the lateral habenula region of the brain, resulting in continuous rewarding signals for the intake of tasty food. They also pinpointed the molecule NPY, produced by the brain during stress, as a significant contributor in this mechanism.

Stress paired with a high-calorie diet amplifies the brain’s rewarding signals for food consumption, thereby triggering weight gain, according to the researchers. This is attributed to the NPY molecule, which the brain produces under stress, and the suppression of satiety responses in the brain’s lateral habenula region. The research stresses the importance of a balanced diet during stressful periods to avoid overeating.

Experiencing stress often makes a high-calorie snack appear comforting. However, this combination has negative implications. Researchers in Sydney assert that stress in conjunction with indulgence in ‘comfort’ foods can cause changes in the brain that encourage excessive eating, increase cravings for sweet, palatable food, and result in weight gain.

The research team from the Garvan Institute discovered that stress overrides the brain’s normal satiety response, leading to uninterrupted reward signals that encourage the consumption of tasty food. This takes place in a region of the brain known as the lateral habenula, which typically curtails these reward signals when activated.

Senior author of the study and visiting scientist at the Garvan Institute, Professor Herzog, stated, “Our research reveals that stress can override the brain’s natural response that limits the pleasure derived from eating – leading to continuous rewards from food intake.” He further added, “Our findings demonstrate that chronic stress, in combination with a high-calorie diet, can result in increasing food intake, as well as a preference for sweet, highly palatable food, thus encouraging weight gain and obesity. This underscores the importance of a healthy diet during times of stress.”

The findings were published in the journal Neuron.

Connecting a stressed brain to weight gain

The team, to understand the driving forces behind these eating habits, used mouse models to study how different brain regions responded to chronic stress under various diets.

Dr. Kenny Chi Kin Ip from the Garvan Institute, the study’s first author, explained, “We found that an area known as the lateral habenula, typically involved in turning off the brain’s reward response, was active in mice on a short-term, high-fat diet to prevent overeating. However, with chronic stress, this part of the brain remained inactive – enabling reward signals to stay active, promoting pleasure eating, no longer responding to satiety regulatory signals.”

Stressed mice on a high-fat diet gained twice as much weight compared to non-stressed mice on the same diet, the researchers found. The NPY molecule, which the brain naturally produces in response to stress, was identified at the core of this weight gain. When researchers inhibited NPY from activating brain cells in the lateral habenula of stressed mice on a high-fat diet, these mice consumed less comfort food, resulting in lesser weight gain.

Comfort food consumption under stress

The team conducted a ‘sucralose preference test’ – allowing mice to choose between drinking water or artificially sweetened water.

According to Professor Herzog, “Stressed mice on a high-fat diet drank three times more sucralose than mice on a high-fat diet alone, suggesting that stress not only increases reward during eating but specifically triggers a craving for sweet, palatable food.” He further added, “Interestingly, this preference for sweetened water was not observed in stressed mice that were on a regular diet.”

Stress disrupting healthy energy balance

Professor Herzog stated, “In stressful situations, it’s easy to expend a lot of energy and a rewarding feeling can calm you down – this is when an energy boost from food is beneficial. But when stress persists over an extended period, it seems to shift the balance, inducing unhealthy eating behaviors in the long run.”

The researchers have identified stress as a significant factor regulating eating habits, capable of overruling the brain’s natural energy balancing mechanism.

Professor Herzog emphasized the implications of their findings, stating, “Our research underscores how much stress can impair a healthy energy metabolism. It serves as a reminder to maintain a stress-free lifestyle, and importantly, to consume a healthy diet and avoid junk food in the face of prolonged stress.”

This study was published in Neuron on 8th June 2023 and was supported by the National Health and Medical Research Council (project grant 1066809). Professor Herzog is a Conjoint Professor at St Vincent’s Clinical School, Faculty of Medicine and Health, UNSW Sydney. Dr. Kenny Chi Kin Ip is a Conjoint Lecturer at the same institution.

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More about Stress-induced overeating

• Garvan Institute of Medical Research
• Role of NPY in appetite regulation and obesity
• Neuron Journal
• Stress and Eating Behaviors
• Effects of stress on eating and the use of food as a coping mechanism