Brain circuit behind satiation offers new target for obesity treatment
The brain functions behind the feelings of fullness that stop us from reaching for another bite are highly complex, but by better understanding the intricacies of these systems scientists hope to uncover new treatments for conditions like obesity. Researchers at Baylor College of Medicine have now identified an entirely new neural circuit that can be targeted to trigger satiation in mice, and even found that an already-approved ADHD drug confers its weight loss effects through this same pathway.
“Many people struggle with weight control, eating more than what the body needs, which adds extra pounds that can lead to obesity and higher risk of serious conditions such as heart disease, stroke and type 2 diabetes,” says study author Dr. Yong Han. “Our lab is interested in improving our understanding of what goes on in the brain during feeding with the hope that our findings might one day help people better control their weight.”
Han and his colleagues used a mix of advanced tools to study the brains of mice during feeding, including optogenetics, neural circuitry mapping down to a cellular level, and live recordings of neural activity. These observations revealed an entirely novel neural circuit that connects two different sets of neurons, one of which produces the neurotransmitter dopamine that is typically associated with feelings of pleasure and motivation.
As the mice were eating, the scientists observed the activity of these two sets of neurons and found that the ones responsible for producing dopamine, called DA-VTA, increased their activity right before the rodents stopped feeding. In subsequent experiments, the scientists genetically inhibited the DA-VTA neurons and found this caused the rodents to continue to eat, making their way through drastically increased portion sizes.
Similar experiments focusing on the second set of downstream DRD1-LPBN neurons, which receive signals from the DA-VTA neurons, found that boosting their activity generated a robust satiation response, causing the mice to promptly terminate their meals. So by targeting these two components of this newly identified neural circuit, the scientists believe they have uncovered a new way to potentially activate feelings of satiation, and one that also highlights a new role for dopamine in the brain.
“Other brain circuits have been proposed to regulate feeding, but the one we discovered is the first to be fully described to regulate portion size via dopamine signaling,” Han says. “Our new study shows that a circuit connecting neurons that produce dopamine, a chemical messenger previously known for the regulation of motivation and pleasure, has a new role in the control of feeding through dynamically regulating the satiety response.”
Interestingly, the scientists found that the weight loss effect seen in the mice as a result of their interventions was the same as that caused by a drug called MPH, which is approved for use as a treatment for ADHD. This sheds further light on the weight loss effects of these types of drugs and how they might be optimized specifically for the purposes of treating conditions like obesity.
“This also has implications for the future development of circuitry-based precision medicine that can deliver weight-reducing results with higher safety and effectiveness," says study author Dr. Qi Wu.
The research was published in the journal Science Advances.
Source: Baylor College of Medicine
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