title: Meta-chlorophenylpiperazine enhances leptin sensitivity in diet-induced obese mice.
abstract: OBJECTIVE
  Most forms of human obesity are characterized by impaired leptin sensitivity and, therefore, the effectiveness of anti-obesity leptin therapy in these leptin-resistant obese patients is marginal. Hence, the development of strategies to increase leptin sensitivity is of high priority in the field of obesity research.
  
  
  METHODS
  We first examined the effects of co-administration of leptin and meta-chlorophenylpiperazine (mCPP), an agonist of 5-HT2C and 5-HT1B receptors, on energy balance in leptin-resistant diet-induced obese (DIO) mice. We further assessed leptin-induced phosphorylation of the STAT-3 (pSTAT3) in various brain regions of DIO mice pretreated with mCPP or in mice genetically lacking 5-HT2C receptors.
  
  
  RESULTS
  Co-administration of mCPP with leptin had an additive effect on reducing body weight in DIO mice. Furthermore, mCPP pretreatment in DIO mice enhanced leptin-induced pSTAT3 in the arcuate nucleus, the ventromedial hypothalamic nucleus, and the ventral premammillary nucleus. Finally, deletion of 5-HT2C receptors significantly blunted leptin-induced pSTAT3 in these same hypothalamic regions.
  
  
  CONCLUSIONS
  Our study provides evidence that drugs, which activate 5-HT2C receptors, could function as leptin sensitizers and be used in combination with leptin to provide additional weight loss in DIO.
authors: Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.|Medical College, Qingdao University, Qingdao, China.
authors: Chunling
authors: C
authors: Yan
authors: Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors: Yongjie
authors: Y
authors: Yang
authors: Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors: Kenji
authors: K
authors: Saito
authors: Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors: Pingwen
authors: P
authors: Xu
authors: Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors: Chunmei
authors: C
authors: Wang
authors: Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors: Antentor Othrell
authors: AO
authors: Hinton
authors: Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors: Xiaofeng
authors: X
authors: Yan
authors: Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors: Qi
authors: Q
authors: Wu
authors: Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors: Qingchun
authors: Q
authors: Tong
authors: Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors: Joel K
authors: JK
authors: Elmquist
authors: Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors: Makoto
authors: M
authors: Fukuda
authors: Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.|Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA.
authors: Yong
authors: Y
authors: Xu
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004032:Diet / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D020738:Leptin / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D058826:Serotonin 5-HT2 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C000599853:5-hydroxytryptamine2C receptor, mouse; D020738:Leptin; D010879:Piperazines; D044405:Receptor, Serotonin, 5-HT2C; D050796:STAT3 Transcription Factor; D058826:Serotonin 5-HT2 Receptor Agonists; C494087:Stat3 protein, mouse; C015068:1-(3-chlorophenyl)piperazine