title: Specific sequences in N termini of apolipoprotein A-IV modulate its anorectic effect.
abstract: Rodent apoA-IV is expressed predominantly in small intestine and also expressed to a small extent in liver and hypothalamus. ApoA-IV has been shown to inhibit food intake in rats when injected centrally. In the current study, we hypothesize that a specific sequence within rat apoA-IV is responsible for mediating the anorectic effect. We use a bacterial expression system to generate truncation mutants (Δ249-371, Δ117-371 and Δ1-61) of rat apoA-IV and assess the ability of various regions of the molecule to inhibit food intake. The results indicate that a responsible sequence exists within the N-terminal 61 amino acids of rat apoA-IV. Synthetic peptides (1-30 EVTSDQVANVMWDYFTQLSNNAKEAVEQLQ, 1-15 EVTSDQVANVMWDYF and 17-30 QLSNNAKEAVEQLQ) were used to specify the region in between residues 1 and 30. A 14-mer peptide (17-30) encompassing this sequence was capable of reducing food intake in a dose-dependent manner whereas a peptide designed on a more C-terminal region (211-232) of apoA-IV (QEKLNHQMEGLAFQMKKNAEEL) failed to exhibit the dose-dependent anorectic effect. The isolation of this sequence provides a valuable tool for future work directed at identifying apoA-IV binding proteins and is a key step for exploring the potential of therapeutic manipulation of food intake via this pathway.
authors.affiliation: Departments of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Pearson
authors.forename: W Sean
authors.initials: WS
authors.lastname: Davidson
authors.forename: Patrick
authors.initials: P
authors.lastname: Tso
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001054:Apolipoproteins A / Q000737:chemistry* / Q000494:pharmacology*; D001067:Appetite Depressants; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D001054:Apolipoproteins A; D001067:Appetite Depressants; D008070:Lipopolysaccharides; D010455:Peptides; D011994:Recombinant Proteins; C022205:apolipoprotein A-IV
keywords: Apolipoprotein A-IV; Food intake; Truncation mutation
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