TrpC5 Mediates Acute Leptin and Serotonin Effects via Pomc Neurons
Copyright policy )TrpC5 Mediates Acute Leptin and Serotonin Effects via Pomc Neurons
The molecular mechanisms underlying acute leptin and serotonin 2C receptor-induced hypophagia remain unclear. Here, we show that neuronal and pro-opiomelanocortin (Pomc)-specific loss of transient receptor potential cation 5 (TrpC5) subunits is sufficient to decrease energy expenditure and increase food intake resulting in elevated body weight. Deficiency of Trpc5 subunits in Pomc neurons is also sufficient to block the anorexigenic effects of leptin and serotonin 2C receptor (Ht2Cr) agonists. The loss of acute anorexigenic effects of these receptors is concomitant with a blunted electrophysiological response to both leptin and Ht2Cr agonists in arcuate Pomc neurons. We also demonstrate that the Ht2Cr agonist lorcaserin-induced improvements in glucose and insulin tolerance are blocked by TrpC5 deficiency in Pomc neurons. Together, our results link TrpC5 subunits in the brain with leptin- and serotonin 2C receptor-dependent changes in neuronal activity, as well as energy balance, feeding behavior, and glucose metabolism.
- PEKING UNION MEDICAL COLLEGE China (People's Republic of)
- Harvard University United States
- The University of Texas Southwestern Medical Center United States
- Chinese Academy of Medical Sciences & Peking Union Medical College China (People's Republic of)
- Korean Association Of Science and Technology Studies Korea (Republic of)
Leptin, Male, obesity, Patch-Clamp Techniques, Pro-Opiomelanocortin, QH301-705.5, transient receptor potential cation channels, leptin, Membrane Potentials, Eating, Mice, Appetite Depressants, Receptor, Serotonin, 5-HT2C, Animals, melanocortin, Biology (General), TRPC Cation Channels, Mice, Knockout, Neurons, diabetes, Body Weight, thermogenesis, patch-clamp, Benzazepines, Glucose Tolerance Test, electrophysiology, serotonin, glycemia, Glucose, Insulin Resistance, Energy Metabolism, lorcaserin, Serotonin 5-HT2 Receptor Agonists
Leptin, Male, obesity, Patch-Clamp Techniques, Pro-Opiomelanocortin, QH301-705.5, transient receptor potential cation channels, leptin, Membrane Potentials, Eating, Mice, Appetite Depressants, Receptor, Serotonin, 5-HT2C, Animals, melanocortin, Biology (General), TRPC Cation Channels, Mice, Knockout, Neurons, diabetes, Body Weight, thermogenesis, patch-clamp, Benzazepines, Glucose Tolerance Test, electrophysiology, serotonin, glycemia, Glucose, Insulin Resistance, Energy Metabolism, lorcaserin, Serotonin 5-HT2 Receptor Agonists
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