Researchers discover new brain circuit that could help fight obesity


Like a good story, food has a beginning, a middle and an end. It starts with the appetite which prompts foraging for food, continues with the consumption of the food, and ends when satiety hits and the food intake is stopped.

At Baylor College of Medicine, Dr Qi Wu, Dr Yong Han and their colleagues discovered new aspects of the latter part of this story that relate to little-known neural circuits and neurotransmitters involved in stopping food consumption. .

The team discovered a new circuit that connects a unique subset of dopamine-producing neurons with neurons downstream in the hindbrain (lower brainstem) and potently suppresses food intake by triggering satiety in mice. They also found that the FDA-approved drug methylphenidate (MPH) mediates its noticeable weight loss effect by activating this particular circuit, opening up the possibility that regulating this circuit could help people control their weight. The study appears in the journal Sciences Advances.

“Many people find it difficult to control their weight, eating more than the body needs, adding extra pounds that can lead to obesity and increased risk of serious illnesses such as heart disease, accidents. cerebrovascular disease and type 2 diabetes, ”said Han, a postdoctoral associate in pediatrics-nutrition in Wu’s lab and first author of this study. “Our lab wants to improve our understanding of what goes on in the brain while eating, with the hope that our findings may one day help people gain better weight control.”

New knowledge on the brain’s regulation of the satiety response:

“The current study is looking at a circuit in the brain that helps to precisely regulate the size of the portion of food consumed,” said Wu, assistant professor of pediatrics-nutrition and corresponding author of the study. “It’s not about how to eat begins, but how it ends. It’s about the fullness response, which is as important as appetite.”

Using several advanced techniques to study neural function, including cell-specific circuit mapping, optogenetics, and real-time recordings of brain activity, the researchers discovered a new neural circuit that connects a unique group of dopamine-producing neurons called DA-VTA with a downstream target. neurons called DRD1-LPBN and regulate food consumption in mice.

The team looked at the activities of both sets of neurons as the mice ate. They observed that the activity of these DA-VTA neurons increased immediately before the animals stopped eating. When the researchers genetically inhibited these neurons, the animals extended their diet, dramatically increasing portion sizes. This suggests that circuit inhibition prevented the satiety response. They also found that enhanced activity of DRD1-LPBN neurons, which receive signals from DA-VTA neurons, robustly generated the end-of-meal response.

The researchers also found that the new circuit induced the weight loss effect associated with taking the drug MPH, which is approved for the alleviation of attention deficit hyperactivity disorder.

Other brain circuits have been proposed to regulate eating, but the one we discovered is the first to be fully described to regulate portion size via dopamine signaling. “” Our new study shows that a circuit connecting neurons that produce dopamine, a chemical messenger previously known to regulate motivation and pleasure, has a new role in controlling eating by dynamically regulating the satiety response. “

Dr Yong Han, Study First Author and Postdoctoral Fellow in Pediatrics-Nutrition, Baylor College of Medicine,

“Our discovery that MPH suppresses diet and reduces body weight in laboratory mice by strengthening the novel dopamine-supported circuit that we discovered, suggests a potential off-label application of a class of MPH and derivatives in the fight against obesity, “Wu said.” It also has implications for the future development of circuit-based precision medicine which can provide weight reduction results with increased safety and efficacy.


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