New study uncovers brain circuit responsible for balancing hunger and pleasure-driven eating
Humans eat for two primary reasons: to satisfy hunger and for the pleasure derived from food, even when they are not hungry. While hunger-driven eating is essential for survival, pleasure-driven consumption can accelerate the onset of obesity and related metabolic disorders. A groundbreaking study published in Nature Metabolism has identified specific neural circuits in the mouse brain that promote hunger-driven feeding while suppressing pleasure-driven eating. These findings offer promising avenues for developing new strategies to combat obesity.
“Ideal feeding habits would balance eating for necessity and for pleasure, minimising the latter. In this study, we identified a group of neurons that regulate balanced feeding in the brain,” stated Dr. Yong Xu, co-corresponding author, professor of paediatrics – nutrition, and associate director for basic sciences at the USDA/ARS Children’s Nutrition Research Center, Baylor College of Medicine.
Previous research has highlighted the role of neurons marked by the GABAergic proenkephalin (Penk) marker, an endogenous opioid hormone, in regulating feeding and body weight balance. However, their specific role in differentiating hunger-driven and pleasure-driven feeding had not been fully understood.
In this study, Xu and his colleagues demonstrated that activating Penk neurons in a brain region called the diagonal band of Broca (DBB) in male mice promotes an ideal feeding pattern, increasing hunger-driven feeding while reducing pleasure-driven eating.
“I was surprised by this finding,” Xu remarked. “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 on the two types of feeding; they increase hunger-driven feeding while decreasing eating for pleasure.”
The researchers delved into the mechanisms behind these opposite effects. They discovered that DBB-Penk neurons project into two different brain areas, each regulating a distinct type of feeding behaviour.
“A subset of DBB-Penk neurons that projects to the paraventricular nucleus of the hypothalamus is preferentially activated upon food presentation during fasting periods, facilitating hunger-driven feeding,” Xu explained. “On the other hand, a separate subset of DBB-Penk neurons that projects to a different brain region, the lateral hypothalamus, is preferentially activated when detecting high-fat, high-sugar (HFHS) foods and inhibits their consumption. This is the first study to show a neural circuit that is activated by a reward, HFHS, but leads to terminating instead of continuing the pleasurable activity.”
Remarkably, mice in which the entire DBB-Penk population had been eliminated showed a significant behavioural change. When given a choice between chow and HFHS diets, these mice reduced their consumption of chow but increased their intake of HFHS foods, leading to rapid development of obesity and metabolic disturbances.
“Our findings indicate that the development of obesity is associated with impaired function of some of these brain circuits in mice,” Xu noted. “We are interested in further investigating molecular markers within these circuits that could be suitable targets for the treatment of human diseases such as obesity.”
The study’s contributors include Hailan Liu, Yongxiang Li, Meng Yu, Olivia Z. Ginnard, Kristine M. Conde, Mengjie Wang, Xing Fang, Hesong Liu, Longlong Tu, Na Yin, Jonathan C. Bean, Junying Han, Yongjie Yang, Qingchun Tong, Benjamin R. Arenkiel, Chunmei Wang, and co-corresponding author Yang He, affiliated with institutions such as Baylor College of Medicine, Baylor’s USDA/ARS Children’s Nutrition Research Center, Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, and the University of Texas Health Science Center at Houston.
