G proteins of the G<sub>12</sub> family expressed by POMC neurons regulate key metabolic functions.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40644553.
- Also identified by DOI 10.1126/sciadv.adu1670 and PMC identifier 12248387.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Proopiomelanocortin (POMC) neurons play a key role in maintaining glucose and energy homeostasis. POMC neurons express many heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors that are linked to different functional classes of G proteins. The potential role of G<sub>12/13</sub> in regulating the function of central POMC neurons remains unknown. To address this question, we used a chemogenetic approach to selectively stimulate G<sub>12/13</sub> signaling in POMC neurons. We found that receptor-mediated activation of G<sub>12/13</sub> signaling in POMC neurons caused notable improvements in glucose homeostasis in lean and obese mice. Stimulation of G<sub>12/13</sub> signaling in POMC neurons also enhanced the physiological actions of leptin. Studies with G<sub>12/13</sub> knockout mice showed that G<sub>12/13</sub> signaling in POMC neurons mediated the beneficial metabolic effects of lorcaserin, an appetite-suppressant drug that selectively activates serotonin 5-HT<sub>2C</sub> receptors. These findings indicate that G<sub>12/13</sub>-coupled receptors expressed by POMC neurons represent potential targets for advanced classes of antidiabetic and appetite-suppressant drugs.
Medical subject headings
- Pro-Opiomelanocortin
- Neurons