HMN 2025: How Dopamine neurons that gas overeating might weaken effectiveness of weight problems medicine

Delicious and intensely palatable meals can enhance the tendency of hedonic consuming, where one consumes meals for the only real objective of deriving pleasure as a substitute of the physique’s vitality wants. Hedonic consuming typically results in consuming past satiety (fullness), which is linked to weight problems. Although meals palatability is carefully linked to hedonic consuming, the neural mechanisms underlying this course of stay largely unclear.

A current study on mice by researchers from the University of California, San Diego and Howard Hughes Medical Institute, Ashburn, recognized a mind circuit between the peri-locus coeruleus and the ventral tegmental space (VTA) chargeable for driving elevated consumption of palatable meals. The work is published within the journal Science.

The VTA^DA or dopamine neurons in VTA, additionally known as the mind’s reward heart, determined the palatability of meals and performed a key position in driving hedonic consuming behaviors and decreasing the effectiveness of weight problems drugs.

Eating behaviors progress in three distinct phases: searching for (initiation), consumption (sustaining), and satiety (terminate feeding). Using cell-specific circuit mapping and optogenetics—a organic method for controlling neurons or cell exercise with gentle—the researchers discovered that the dopamine neurons in VTA didn’t impression the food-seeking conduct.

They had been solely triggered throughout meals consumption, and their exercise elevated or decreased in response to the tastiness of the meals. The researchers famous that activating the neurons with optogenetics throughout consuming extended meals consumption, much like the impact of constructing meals extra palatable, however inhibiting these neurons diminished consumption with out affecting the initiation of consuming.

The exercise of the dopamine neurons in the course of the consumption of meals was suppressed by semaglutide, a glucagon-like peptide receptor 1 (GLP-1R) agonist that mimics the mind’s satiety indicators and is usually used as an antiobesity drug.

Mice handled with semaglutide ate much less and exhibited low VTA^DA neuron exercise; nonetheless, artificially activated neurons throughout meals consumption overcame the appetite-reducing impact of semaglutide and enhanced each meals consumption and consuming length.

The researchers observed that as mice misplaced weight on semaglutide, VTA^DA neuron exercise elevated, and so did the consumption of palatable meals. This commentary may assist clarify why some weight problems drugs containing semaglutide fail to utterly suppress overeating in sure people. They additionally discovered that this anti-semaglutide conduct could be successfully reversed by focused inhibition of VTA^DA neurons.

The mechanism by which VTA^DA neurons regulate the length of meals consumption gives key insights into how palatable meals influences urge for food. Exploring the interactions between these neurons and totally different elements of the mind may open up new avenues for creating methods to fight weight problems and different metabolic problems.

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