AIMS: 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. MAIN 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. KEY FINDINGS: 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. SIGNIFICANCE: 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.
AIMS: 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. MAIN 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. KEY FINDINGS: 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. SIGNIFICANCE: 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: Hannu Turpeinen; Anna Oksanen; Virpi Kivinen; Sampo Kukkurainen; Annemari Uusimäki; Mika Rämet; Mataleena Parikka; Vesa P Hytönen; Matti Nykter; Marko Pesu Journal: J Biol Chem Date: 2013-10-31 Impact factor: 5.157
Authors: Jeeyoung Lee; Arthur B Karnuah; Romdhane Rekaya; Nicholas B Anthony; Samuel E Aggrey Journal: Mol Genet Genomics Date: 2015-03-18 Impact factor: 3.291