Understanding the role of the brain in hedonic eating—the act of eating for pleasure rather than for physiological need—has been a popular endeavor. Researchers at the University of California, San Diego (UCSD), identified how a brain circuit involving dopamine and glucagon-like peptide receptor 1, which suppresses appetite, impacts palatability and hedonic eating.
Hedonic eating is often linked to obesity and many studies have shown a more complex relationship between eating, obesity, and brain function. While neural circuits involved in food-seeking behavior and satiety are known, Zhenggang Zhu, PhD, a postdoctoral researcher at UCSD, and colleagues investigated how the ventral tegmental area (VTA) dopamine neurons regulate the consumption of pleasurable foods using cell specific circuit mapping, optogenetics, and in vivo imaging.
The findings, published in Science in a paper titled, “Hedonic eating is controlled by dopamine neurons that oppose GLP-1R satiety,” reveal that neurons in the VTA sustain the consumption of pleasurable or palatable foods and may help explain why certain obesity medications, such as GLP-1 agonists, do not fully suppress overeating in some individuals.
Using mice, the team found that while the VTA dopamine neurons aren’t involved in food-seeking behaviors, they were activated during consumption and increased activity in response to food palatability. However, activation of the neurons when mice were not eating didn’t change their behavior.
“When we optogenetically boosted VTA dopamine neuron activity specifically during consumption, food intake was prolonged in a manner similar to the effect of increasing food palatability,” the authors wrote. “Conversely, inhibition of VTA dopamine neurons reduced consumption.”
GLP-1 agonists, including semaglutide, mimic satiety signals in the brain, leading to reduced appetite. These drugs are increasingly used to treat obesity in humans. Mice treated with semaglutide exhibited reduced VTA dopamine neuron activity and ate less.
However, optogenetically activating neurons counteracted the appetite suppression of semaglutide. The researchers also found that “as mice lost weight on semaglutide, VTA dopamine neuron activity increased, as did palatable food intake, which could be reversed by inhibiting VTA dopamine neurons.”
“This study clarifies the involvement of VTA dopamine neurons in the consummatory phase of hedonic food intake,” the authors wrote.
Further analysis identified a neural connection between the peri-locus coeruleus and the VTA, which influences VTA dopamine activity. Specifically, glutamate-releasing neurons in the peri-locus coeruleus were found to indirectly suppress VTA dopamine neurons through inhibitory intermediaries.
The authors concluded: “Taken together, these results highlight the importance of VTA dopamine neurons in mediating consumption behaviors, their role in semaglutide effects on palatable food intake, and the potential for modulation of these neurons to reverse the elevated consumption of sweet foods after weight loss on semaglutide.”
The results provide insight into an explanation for observations in human patients taking GLP-1 agonists who experience reduced appetite suppression over time. If the mechanism seen in mice is parallel in humans, then targeting the VTA neurons may improve semaglutide treatment effectiveness in some humans.
Further exploration of this neural circuit is important to identify the interaction between VTA neurons, other brain regions, and eating behaviors. In fact, another recent study explored a related VTA neural circuit involving neurotensin. Exploration of all facets of neural circuits related to how the brain responds to hedonic eating may help combat obesity and related metabolic disorders.
“Future work that aims to minimize such adaptation could offer a promising avenue for the development of adjunct therapies to broaden the group of individuals for whom GLP-1 agonist treatment is effective,” wrote Dana Small, PhD, in a related Science Perspective article.