Bile acid-regulated peroxisome proliferator-activated receptor-α (PPARα) activity underlies circadian expression of intestinal peptide absorption transporter PepT1/Slc15a1

Ayako Okamura, Satoru Koyanagi, Adila Dilxiat, Naoki Kusunose, Jia Jun Chen, Naoya Matsunaga, Shigenobu Shibata, Shigehiro Ohdo

    Research output: Contribution to journalArticle

    14 Citations (Scopus)

    Abstract

    Digested proteins are mainly absorbed as small peptides composed of two or three amino acids. The intestinal absorption of small peptides is mediated via only one transport system: the proton-coupled peptide transporter-1 (PepT1) encoded from the soluble carrier protein Slc15a1. In mammals, intestinal expression of PepT1/Slc15a1 oscillates during the daily feeding cycle. Although the oscillation in the intestinal expression of PepT1/Slc15a1 is suggested to be controlled by molecular components of circadian clock, we demonstrated here that bile acids regulated the oscillation of PepT1/Slc15a1 expression through modulating the activity of peroxisome proliferator-activated receptor α (PPARα). Nocturnally active mice mainly consumed their food during the dark phase. PPARα activated the intestinal expression of Slc15a1 mRNA during the light period, and protein levels of PepT1 peaked before the start of the dark phase. After food intake, bile acids accumulated in intestinal epithelial cells. Intestinal accumulated bile acids interfered with recruitment of co-transcriptional activator CREB-binding protein/p300 on the promoter region of Slc15a1 gene, thereby suppressing PPARα-mediated transactivation of Slc15a1. The timedependent suppression of PPARα-mediated transactivation by bile acids caused an oscillation in the intestinal expression of PepT1/Slc15a1 during the daily feeding cycle that led to circadian changes in the intestinal absorption of small peptides. These findings suggest a molecular clock-independent mechanism by which bile acid-regulated PPARα activity governs the circadian expression of intestinal peptide transporter.

    Original languageEnglish
    Pages (from-to)25296-25305
    Number of pages10
    JournalJournal of Biological Chemistry
    Volume289
    Issue number36
    DOIs
    Publication statusPublished - 2014

    Fingerprint

    Peroxisome Proliferator-Activated Receptors
    Intestinal Absorption
    Bile Acids and Salts
    Peptides
    Transcriptional Activation
    Period Circadian Proteins
    CREB-Binding Protein
    Clocks
    Circadian Clocks
    Mammals
    Genetic Promoter Regions
    Protons
    Carrier Proteins
    Eating
    Epithelial Cells
    peptide permease
    intestinal peptide-proton cotransporter
    Light
    Amino Acids
    Food

    ASJC Scopus subject areas

    • Biochemistry
    • Cell Biology
    • Molecular Biology

    Cite this

    Bile acid-regulated peroxisome proliferator-activated receptor-α (PPARα) activity underlies circadian expression of intestinal peptide absorption transporter PepT1/Slc15a1. / Okamura, Ayako; Koyanagi, Satoru; Dilxiat, Adila; Kusunose, Naoki; Chen, Jia Jun; Matsunaga, Naoya; Shibata, Shigenobu; Ohdo, Shigehiro.

    In: Journal of Biological Chemistry, Vol. 289, No. 36, 2014, p. 25296-25305.

    Research output: Contribution to journalArticle

    Okamura, Ayako ; Koyanagi, Satoru ; Dilxiat, Adila ; Kusunose, Naoki ; Chen, Jia Jun ; Matsunaga, Naoya ; Shibata, Shigenobu ; Ohdo, Shigehiro. / Bile acid-regulated peroxisome proliferator-activated receptor-α (PPARα) activity underlies circadian expression of intestinal peptide absorption transporter PepT1/Slc15a1. In: Journal of Biological Chemistry. 2014 ; Vol. 289, No. 36. pp. 25296-25305.
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    abstract = "Digested proteins are mainly absorbed as small peptides composed of two or three amino acids. The intestinal absorption of small peptides is mediated via only one transport system: the proton-coupled peptide transporter-1 (PepT1) encoded from the soluble carrier protein Slc15a1. In mammals, intestinal expression of PepT1/Slc15a1 oscillates during the daily feeding cycle. Although the oscillation in the intestinal expression of PepT1/Slc15a1 is suggested to be controlled by molecular components of circadian clock, we demonstrated here that bile acids regulated the oscillation of PepT1/Slc15a1 expression through modulating the activity of peroxisome proliferator-activated receptor α (PPARα). Nocturnally active mice mainly consumed their food during the dark phase. PPARα activated the intestinal expression of Slc15a1 mRNA during the light period, and protein levels of PepT1 peaked before the start of the dark phase. After food intake, bile acids accumulated in intestinal epithelial cells. Intestinal accumulated bile acids interfered with recruitment of co-transcriptional activator CREB-binding protein/p300 on the promoter region of Slc15a1 gene, thereby suppressing PPARα-mediated transactivation of Slc15a1. The timedependent suppression of PPARα-mediated transactivation by bile acids caused an oscillation in the intestinal expression of PepT1/Slc15a1 during the daily feeding cycle that led to circadian changes in the intestinal absorption of small peptides. These findings suggest a molecular clock-independent mechanism by which bile acid-regulated PPARα activity governs the circadian expression of intestinal peptide transporter.",
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    AU - Okamura, Ayako

    AU - Koyanagi, Satoru

    AU - Dilxiat, Adila

    AU - Kusunose, Naoki

    AU - Chen, Jia Jun

    AU - Matsunaga, Naoya

    AU - Shibata, Shigenobu

    AU - Ohdo, Shigehiro

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