title: Methylnaltrexone potentiates body weight and fat reduction with leptin.
abstract: OBJECTIVE
  Leptin increases energy expenditure by enhancing systemic and brown adipose metabolism. In a neonatal rat model, retroperitoneal fat pad weight decreased significantly in leptin-treated animals, which reduced body weight. As opioids increase feeding, opioid antagonists may decrease food intake and body weight. However, interactions between leptin and the activity of peripheral opioids on body weight and fat accumulation have not been investigated. In this study, the authors evaluated the effects of naloxone (a nonselective opioid antagonist) and methylnaltrexone (a peripherally acting opioid antagonist) on the action of leptin in neonatal rats.
  
  
  RESULTS
  Compared with control, the weight gain of pups given a single daily intraperitoneal injection of leptin 0.5 mg/kg, leptin 0.5 mg/kg plus naloxone 0.3 mg/kg, or leptin 0.5 mg/kg plus methylnaltrexone 3.0 mg/kg for 8 consecutive days was significantly reduced (all p < 0.01). Naloxone or methylnaltrexone significantly potentiated leptin's effect on body weight (p < 0.05 or p < 0.01, respectively). After coadministration of leptin plus naloxone or leptin plus methylnaltrexone, weight reduction in the right retroperitoneal fat pads was also significant compared with the reduction after leptin alone (p < 0.05 or p < 0.01, respectively).
  
  
  CONCLUSIONS
  The data suggest the existence of a peripheral opioid-related mechanism in leptin-active modulation of body weight.
authors.affiliation: Department of Anesthesia & Critical Care, Pritzker School of Medicine, University of Chicago, Illinois, USA
authors.forename: Chun-Su
authors.initials: CS
authors.lastname: Yuan
authors.forename: Shi
authors.initials: S
authors.lastname: Sun
authors.forename: Anoja
authors.initials: A
authors.lastname: Attele
authors.forename: Chong-Zhi
authors.initials: CZ
authors.lastname: Wang
authors.forename: Robin
authors.initials: R
authors.lastname: Tong
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Israel
mesh_terms: D050154:Adiposity / Q000187:drug effects*; D000818:Animals; D000831:Animals, Newborn; D004357:Drug Synergism; D007274:Injections, Intraperitoneal; D050152:Intra-Abdominal Fat / Q000033:anatomy & histology / Q000187:drug effects*; D020738:Leptin / Q000008:administration & dosage / Q000494:pharmacology*; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015431:Weight Loss / Q000187:drug effects*
chemical_list: D020738:Leptin; D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds; C032257:methylnaltrexone; D009271:Naltrexone