Specific sequences in N termini of apolipoprotein A-IV modulate its anorectic effect

Fei Wang, Kevin J. Pearson, W. Sean Davidson, Patrick Tso

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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.

Original languageEnglish
Pages (from-to)136-142
Number of pages7
JournalPhysiology and Behavior
Volume120
DOIs
StatePublished - Aug 5 2013

Bibliographical note

Funding Information:
This work was supported by grants from the National Institute of Health : DK076928 , DK092138 , DK059630 (to P.T.), and HL67093 , HL82734 (to W. S. D.)

Keywords

  • Apolipoprotein A-IV
  • Food intake
  • Truncation mutation

ASJC Scopus subject areas

  • Experimental and Cognitive Psychology
  • Behavioral Neuroscience

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