Central 5-HTR2C in the Control of Metabolic Homeostasis

The 5-hydroxytryptamine 2C receptor (5-HTR2C) is a class G protein-coupled receptor (GPCR) enriched in the hypothalamus and the brain stem, where it has been shown to regulate energy homeostasis, including feeding and glucose metabolism. Accordingly, 5-HTR2C has been the target of several anti-obesity drugs, though the associated side effects greatly curbed their clinical applications. Dissecting the specific neural circuits of 5-HTR2C-expressing neurons and the detailed molecular pathways of 5-HTR2C signaling in metabolic regulation will help to develop better therapeutic strategies towards metabolic disorders. In this review, we introduced the regulatory role of 5-HTR2C in feeding behavior and glucose metabolism, with particular focus on the molecular pathways, neural network, and its interaction with other metabolic hormones, such as leptin, ghrelin, insulin, and estrogens. Moreover, the latest progress in the clinical research on 5-HTR2C agonists was also discussed.

Automated summary

5-HTR2C plays a key role in regulating energy homeostasis and metabolic disorders, with potential therapeutic implications in anti-obesity drugs. Understanding the neural circuits and molecular pathways of 5-HTR2C signaling is crucial for developing effective treatment strategies. Additionally, the interaction between 5-HTR2C and other metabolic hormones, such as leptin and insulin, is an important area of research.