Brain Circuit May Prevent Obesity by Controlling Eating Habits

Discovery of a novel brain circuit is found to connect a unique subset of dopamine-producing neurons with downstream neurons in the hindbrain (lower brainstem) and potently suppresses food intake by triggering satiation in mice as per a study at the Baylor College of Medicine, published in the journal Sciences Advances.

The study team uncovered new aspects of the little-known neural circuits and neurotransmitters involved in precisely regulating and ending food consumption. Dopamine is a type of chemical messenger (neurotransmitters) in the brain that is responsible mainly for reward actions, regulation of motivation, and pleasure.

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‘Discovery of a novel circuit is found to control eating and thereby help regulate obesity. The circuit connects a unique subset of dopamine-producing neurons with downstream neurons in the hindbrain (lower brainstem) and potently suppresses food intake by triggering satiation in mice model study. A FDA-approved drug MPH is additionally found to suppress feeding and reduces body weight in laboratory mice by strengthening the dopamine-supported novel circuit. ’

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The weight loss mechanism of a FDA-approved drug methylphenidate (MPH for mitigation of attention deficit hyperactivity disorder) is also found to be mediated by activating this particular circuit. This opens the possibility that regulating this circuit might help people control weight.

"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. 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," says Dr. Yong Han, a postdoctoral associate in pediatrics-nutrition in the Wu lab and the first author of this study.

Brain Regulation on the Satiation Response

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The present study utilized several advanced techniques to study the neural function of the two sets of neurons while the mice were eating, including cell-specific circuitry mapping, optogenetics, and real-time recordings of brain activity.

It was discovered that a novel neural circuit connects a unique group of dopamine-producing neurons called DA-VTA with downstream target neurons known as DRD1-LPBN and regulates food consumption in mice.

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The activity of these DA-VTA neurons increased immediately before the animals stopped eating. And enhancing the activity of the DRD1-LPBN neurons (which receive signals from the DA-VTA neurons), robustly generated the response of meal termination.

By genetically inhibiting these neurons, the animals were found to prolong their feeding, and drastically increase the portion size. This states that inhibiting the circuit prevented the satiation response.

"Our finding that MPH suppresses feeding and reduces body weight in laboratory mice by strengthening the dopamine-supported novel circuit we discovered, suggests a potential off-label application of a class of MPH and derivatives in tackling 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 Dr. Qi Wu, who guided the study at Baylor College of Medicine.

Source-Medindia