title: PCSK2-null mice exhibit delayed intestinal motility, reduced refeeding response and altered plasma levels of several regulatory peptides.
abstract: OBJECTIVE
  To examine the effects of global lack of proprotein convertase subtilisin/kexin 2 (PCSK2) in mouse on intestinal motility, post-fast refeeding response and levels of several PCSK-generated peptides known to regulate food intake and processing.
  
  
  METHODS
  Using male and female PCSK2 knockout (KO) and wild-type (WT) mice, intestinal motility was assessed by determining the percent of intestinal length travelled by a charcoal-dyed meal following an oral gavage; the refeeding response by measuring the amount of meal consumed following an overnight fast; the levels of the regulatory peptides by enzyme immunoassays or immunoblotting.
  
  
  RESULTS
  Relative to same-gender WT mice, KO mice exhibited delayed intestinal transit (P<0.001 in females; P<0.05 in males). Their post-fast feeding response was reduced in females during the first hour of refeeding (P<0.05). The circulating level of substance P (SP) was lower (P<0.001 in females; P<0.05 in males); it was higher for somatostatin (SS) (P<0.001 in females; P<0.05 in males) and GLP-1 (P<0.001 in females; P<0.01 in males) and GLP-2 (P<0.001 in both genders); it was higher for peptide YY (PYY) in female mice only (P<0.01). Processing of brain proneuropeptide Y was impaired in both genders.
  
  
  CONCLUSIONS
  The alterations in intestinal motility and post-fast refeeding response observed in PCSK2-KO mice correlate with changes in the circulating and tissue levels of the regulatory peptides tested, suggesting that PCSK2 is needed for normal food intake and processing.
authors.affiliation: Chronic Disease, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Gagnon
authors.forename: Janice
authors.initials: J
authors.lastname: Mayne
authors.forename: Andrew
authors.initials: A
authors.lastname: Chen
authors.forename: Angela
authors.initials: A
authors.lastname: Raymond
authors.forename: John
authors.initials: J
authors.lastname: Woulfe
authors.forename: Majambu
authors.initials: M
authors.lastname: Mbikay
authors.forename: Michel
authors.initials: M
authors.lastname: Chrétien
mesh_terms: D000818:Animals; D002766:Cholecystokinin / Q000097:blood*; D005247:Feeding Behavior / Q000502:physiology*; D005260:Female; D005769:Gastrointestinal Motility / Q000235:genetics*; D052216:Glucagon-Like Peptide 1 / Q000097:blood*; D007118:Immunoassay; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000097:blood*; D045706:Proprotein Convertase 2 / Q000235:genetics*
chemical_list: D010446:Peptide Fragments; C053841:cholecystokinin (1-14); D052216:Glucagon-Like Peptide 1; D002766:Cholecystokinin; C473668:Pcsk2 protein, mouse; D045706:Proprotein Convertase 2