Gα
| Autor: | Eun-Seon, Yoo, Li, Li, Lin, Jia, Caleb C, Lord, Charlotte E, Lee, Shari G, Birnbaum, Claudia R, Vianna, Eric D, Berglund, Kathryn A, Cunningham, Yong, Xu, Jong-Woo, Sohn, Chen, Liu |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Mice Knockout Neurons Serotonin Mice 129 Strain Hunger Hypothalamus Feeding Behavior GTP-Binding Protein alpha Subunits Gi-Go Article Anorexia Mice Inbred C57BL Mice Serotonin Agents nervous system Appetite Depressants Models Animal Potassium Receptor Serotonin 5-HT2C Animals Energy Metabolism Paraventricular Hypothalamic Nucleus |
| Zdroj: | Cell reports |
| ISSN: | 2211-1247 |
| Popis: | SUMMARY The anorexigenic effect of serotonergic compounds has largely been attributed to activation of serotonin 2C receptors (Htr2cs). Using mouse genetic models in which Htr2c can be selectively deleted or restored (in Htr2c-null mice), we investigate the role of Htr2c in forebrain Sim1 neurons. Unexpectedly, we find that Htr2c acts in these neurons to promote food intake and counteract the anorectic effect of serotonergic appetite suppressants. Furthermore, Htr2c marks a subset of Sim1 neurons in the paraventricular nucleus of the hypothalamus (PVH). Chemogenetic activation of these neurons in adult mice suppresses hunger, whereas their silencing promotes feeding. In support of an orexigenic role of PVH Htr2c, whole-cell patch-clamp experiments demonstrate that activation of Htr2c inhibits PVH neurons. Intriguingly, this inhibition is due to Gαi/o-dependent activation of ATP-sensitive K+ conductance, a mechanism of action not identified previously in the mammalian nervous system. Graphical Abstract In brief Yoo et al. show that Htr2c, the target of a former weight loss drug, can inhibit and promote food intake by coupling with distinct intracellular signaling events in different hypothalamic neurons. These findings may help explain the rather modest anti-obesity effects of Htr2c agonists. |
| Databáze: | OpenAIRE |
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