title: Spexin is a novel human peptide that reduces adipocyte uptake of long chain fatty acids and causes weight loss in rodents with diet-induced obesity.
abstract: OBJECTIVE
  Microarray studies identified Ch12:orf39 (Spexin) as the most down-regulated gene in obese human fat. Therefore, we examined its role in obesity pathogenesis.
  
  
  METHODS
  Spexin effects on food intake, meal patterns, body weight, respiratory exchange ratio (RER), and locomotor activity were monitored electronically in C57BL/6J mice or Wistar rats with diet-induced obesity (DIO). Its effects on adipocyte [(3)H]-oleate uptake were determined.
  
  
  RESULTS
  In humans, Spexin gene expression was down-regulated 14.9-fold in obese omental and subcutaneous fat. Circulating Spexin changed in parallel, correlating (r = -0.797) with Leptin. In rats, Spexin (35 µg/kg/day SC) reduced caloric intake ∼32% with corresponding weight loss. Meal patterns were unaffected. In mice, Spexin (25 µg/kg/day IP) significantly reduced the RER at night, and increased locomotion. Spexin incubation in vitro significantly inhibited facilitated fatty acid (FA) uptake into DIO mouse adipocytes. Conditioned taste aversion testing (70 µg/kg/day IP) demonstrated no aversive Spexin effects.
  
  
  CONCLUSIONS
  Spexin gene expression is markedly down-regulated in obese human fat. The peptide produces weight loss in DIO rodents. Its effects on appetite and energy regulation are presumably central; those on adipocyte FA uptake appear direct and peripheral. Spexin is a novel hormone involved in weight regulation, with potential for obesity therapy.
authors.affiliation: Department of Medicine, Columbia University Medical Center, New York, New York, 10032, USA.
authors.forename: José L
authors.initials: JL
authors.lastname: Walewski
authors.forename: Fengxia
authors.initials: F
authors.lastname: Ge
authors.forename: Harrison
authors.initials: H
authors.lastname: Lobdell
authors.forename: Nancy
authors.initials: N
authors.lastname: Levin
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Schwartz
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Vasselli
authors.forename: Afons
authors.initials: A
authors.lastname: Pomp
authors.forename: Gregory
authors.initials: G
authors.lastname: Dakin
authors.forename: Paul D
authors.initials: PD
authors.lastname: Berk
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015536:Down-Regulation; D004435:Eating / Q000187:drug effects; D002149:Energy Intake / Q000502:physiology*; D005227:Fatty Acids / Q000493:pharmacokinetics*; D005247:Feeding Behavior; D006801:Humans; D020738:Leptin / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000378:metabolism*; D019301:Oleic Acid / Q000378:metabolism; D036361:Peptide Hormones / Q000494:pharmacology*; D040081:Protein Array Analysis; D051381:Rats; D017208:Rats, Wistar; D015431:Weight Loss / Q000502:physiology*
chemical_list: D005227:Fatty Acids; D020738:Leptin; D036361:Peptide Hormones; C550448:SPX protein, rat; D019301:Oleic Acid