A Brain Reward Circuit Inhibited By Next-Generation Weight Loss Drugs.

Glucagon-like peptide-1 receptor agonists (GLP1RAs) effectively reduce body weight and improve metabolic outcomes, yet established peptide-based therapies require injections and complex manufacturing. Small-molecule GLP1RAs promise oral bioavailability and scalable manufacturing, but their selective binding to human versus rodent receptors has limited mechanistic studies. Here, we developed humanized GLP1R mouse models to investigate how small-molecule GLP1RAs influence feeding behavior.

Molecular connectomics reveals a glucagon-like peptide 1-sensitive neural circuit for satiety.

Liraglutide and other glucagon-like peptide 1 receptor agonists (GLP-1RAs) are effective weight loss drugs, but how they suppress appetite remains unclear. One potential mechanism is by activating neurons that inhibit the hunger-promoting Agouti-related peptide (AgRP) neurons of the arcuate hypothalamus (Arc). To identify these afferents, we developed a method combining rabies-based connectomics with single-nucleus transcriptomics.

Molecular Connectomics Reveals a Glucagon-Like Peptide 1 Sensitive Neural Circuit for Satiety.

Liraglutide and other agonists of the glucagon-like peptide 1 receptor (GLP-1RAs) are effective weight loss drugs, but how they suppress appetite remains unclear. One potential mechanism is by activating neurons which inhibit hunger-promoting Agouti-related peptide (AgRP) neurons of the arcuate hypothalamus (Arc). To identify these afferents, we developed a method combining rabies-based connectomics with single-nuclei transcriptomics.

The hypothalamic mechanism of neuropeptide S-induced satiety in Japanese quail (Coturnix japonica) involves the paraventricular nucleus and corticotropin-releasing factor.

Neuropeptide S (NPS), a 20-amino acid neuropeptide, is produced in the brain and is associated with appetite suppression.Our group was the first to report this anorexigenic effect in birds using chicken as a model, although a hypothalamic molecular mechanism remains to be elucidated. Thus, we designed the present study using Japanese quail(Coturnix japonica).