Proenkephalin opioid peptide linked to comfort food overeating behavior, study finds

28 Nov 2023 --- Researchers at Virginia Tech Carilion’s (VTC) Fralin Biomedical Research Institute have identified the proenkephalin (Penk) molecule in the hypothalamus as the catalyst for emotional overeating. Penk, an endogenous opioid polypeptide hormone, has been connected to various emotional behaviors such as fear conditioning and anxiety.

The scientists set out to study the molecule based on the hypothesis that it already plays a role in stress and eating. Proenkephalin is found in many parts of the brain, but there needs to be more research on its role in the hypothalamus — the center for regulating eating behavior.

“Something about this molecule is critical to inducing overconsumption after a threat. We have much more to learn about this molecule, but we found its location, and it could be a good starting point,” says Sora Shin, assistant professor at the Fralin Biomedical Research Institute at VTC. 

Triggered by stress
The polypeptide comes into play following an anxiety-inducing situation or a psychological reaction to a threat called a fight or flight response. Hours after an event like this, a person can strongly desire processed comfort foods. The research discovery could provide a possible target for therapy to alleviate emotionally triggered eating. 

Previous studies showed that stress-induced maladaptive responses of feeding-related neural circuits or neuroendocrine systems may cause appetite changes. However, what still needs to be scientifically determined is how neural circuits or hormonal dynamics are involved and how their interactions adapt to threatening stimuli that trigger emotional eating.

“We don’t always eat because we are hungry and we have certain physical needs. Whenever we get stressed or feel some threat, then it can also trigger our eating motivation. We think this molecule is the culprit,” says Shin.

Maladaptive responses
Stress hormones, particularly corticosterone, can exert appetite-stimulating effects. Activation of the hypothalamic-pituitary-adrenal axis elevates corticosterone levels following the onset of stressful events. 

This increase typically returns to baseline levels within hours or days after the threatening situation ends. Given that corticosterone receptors are highly expressed in multiple hypothalamic subregions, it is plausible that threat-triggered elevations interact with specific hypothalamic neurons, sensitizing the neuronal responses to palatable foods. 

The research published in Nature Communications uses the odor of a natural predator to induce the desired reaction, which can then be analyzed and measured.The goal of the study is to get closer to developing therapies to remedy overeating. 

Emotional eating relieves stress and tension and provides a sense of control. However, the pathway of how a threat signals your brain to want comfort food has remained a mystery to scientists.

Threats can trigger maladaptive responses that persist well after the situation abates, including reactions such as cravings for palatable foods or pathological eating habits. Identifying the post-stress factors will significantly help the development of therapeutics to combat problematic eating habits such as binge eating or bulimic episodes.

Olfactory method
The odor of a natural predator triggered a threat response in the test mice and 24 hours later, the mice exhibited a negative emotional state and overeating behavior. Neurons in their brains showed sensitivity to consumption of high-fat foods.

To confirm the molecule’s role in stress-induced eating, the researchers activated the same neurons artificially with light, stimulating a genetically encoded molecule expressed in the neuronal cell’s membrane without the predator scent and saw a similar response.

In addition, researchers from the Osaka Metropolitan University in Japan investigated what stimulates the brain to cause overeating and discovered a genetic mechanism associated with high-calorie, food-fueled obesity.

By Inga de Jong