title: 5-HT2CRs expressed by pro-opiomelanocortin neurons regulate energy homeostasis.
abstract: Drugs activating 5-hydroxytryptamine 2C receptors (5-HT2CRs) potently suppress appetite, but the underlying mechanisms for these effects are not fully understood. To tackle this issue, we generated mice with global 5-HT2CR deficiency (2C null) and mice with 5-HT2CRs re-expression only in pro-opiomelanocortin (POMC) neurons (2C/POMC mice). We show that 2C null mice predictably developed hyperphagia, hyperactivity, and obesity and showed attenuated responses to anorexigenic 5-HT drugs. Remarkably, all these deficiencies were normalized in 2C/POMC mice. These results demonstrate that 5-HT2CR expression solely in POMC neurons is sufficient to mediate effects of serotoninergic compounds on food intake. The findings also highlight the physiological relevance of the 5-HT2CR-melanocortin circuitry in the long-term regulation of energy balance.
authors.affiliation: Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.forename: Juli E
authors.initials: JE
authors.lastname: Jones
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kohno
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Williams
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Lee
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: Choi
authors.forename: Jason G
authors.initials: JG
authors.lastname: Anderson
authors.forename: Lora K
authors.initials: LK
authors.lastname: Heisler
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Zigman
authors.forename: Bradford B
authors.initials: BB
authors.lastname: Lowell
authors.forename: Joel K
authors.initials: JK
authors.lastname: Elmquist
mesh_terms: D000818:Animals; D001066:Appetite / Q000187:drug effects / Q000235:genetics; D001067:Appetite Depressants / Q000494:pharmacology; D001069:Appetite Regulation / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics*; D006706:Homeostasis / Q000235:genetics*; D006963:Hyperphagia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D009434:Neural Pathways / Q000166:cytology / Q000378:metabolism; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics*; D012701:Serotonin / Q000378:metabolism*
chemical_list: D001067:Appetite Depressants; D044405:Receptor, Serotonin, 5-HT2C; D012701:Serotonin; D011333:Pro-Opiomelanocortin