A new study published in Nature Metabolism has identified a neural circuit in mice that promotes hunger-driven feeding while suppressing pleasure-driven eating. This discovery could have significant implications for understanding and potentially treating obesity and related metabolic disorders.
The Dual Nature of Eating Behavior
People eat for two main reasons: to satisfy hunger or for pleasure. While hunger-driven eating is essential for survival, excessive pleasure-driven eating can contribute to obesity and associated health problems. The research team, led by Dr. Yong Xu from Baylor College of Medicine, aimed to understand the brain mechanisms that regulate these two types of feeding behaviors.
“Ideal feeding habits would balance eating for necessity and for pleasure, minimizing the latter,” said Dr. Xu. “In this study we identified a group of neurons that regulates balanced feeding in the brain.”
The researchers focused on neurons identified by the GABAergic proenkephalin (Penk) marker, an endogenous opioid hormone. Previous studies had shown that these neurons play a role in feeding and body weight balance, but their specific contribution to hunger- and pleasure-driven feeding was unclear.
A Surprising Discovery: Opposite Effects on Feeding Behaviors
The study revealed that activating Penk neurons in the diagonal band of Broca (DBB) region of the mouse brain had opposite effects on the two types of feeding behaviors. Dr. Xu expressed surprise at this finding, noting, “We and other groups had previously shown that certain groups of neurons affect both feeding types in the same way – they either increase or decrease both types. Here we found that activating DBB-Penk neurons has opposite effects in the two types of feeding, they increase hunger-driven feeding while decreasing eating for pleasure.”
Further investigation uncovered the mechanism behind these contrasting effects. The DBB-Penk neurons project to two different brain areas:
1. A subset projecting to the paraventricular nucleus of the hypothalamus is activated during fasting, promoting hunger-driven feeding.
2. Another subset projecting to the lateral hypothalamus is activated when detecting high-fat, high-sugar foods, inhibiting their consumption.
This is the first study to identify a neural circuit that is activated by a reward (high-fat, high-sugar food) but leads to terminating rather than continuing the pleasurable activity.
Why it matters: Understanding the neural circuits that regulate different types of eating behaviors could lead to new strategies for combating obesity and related metabolic disorders. By potentially targeting these specific circuits, future treatments might be able to promote a healthier balance between hunger-driven and pleasure-driven eating.
The study also found that mice lacking the entire DBB-Penk neuron population showed a preference for high-fat, high-sugar diets over regular chow, leading to accelerated obesity and metabolic disturbances. This suggests that impaired function of these brain circuits may contribute to the development of obesity in mice, and potentially in humans.
Looking ahead, the researchers plan to investigate molecular markers within these circuits that could serve as targets for treating obesity in humans. As obesity rates continue to rise globally, this research provides a promising avenue for developing more targeted and effective interventions.
The findings also raise intriguing questions about the evolution of these neural circuits and how they may have been shaped by our ancestral environment. Understanding how these circuits function in humans and how they may be influenced by modern diets and lifestyles could provide valuable insights into the obesity epidemic and potential strategies for promoting healthier eating habits.
