Oleic acid-induced ADRP expression requires both AP-1 and PPAR response elements, and is reduced by Pycnogenol through mRNA degradation in NMuLi liver cells

Bin Fan, Shoichiro Ikuyama, Jian Qiu Gu, Ping Wei, Jun Ichi Oyama, Toyoshi Inoguchi, Junji Nishimura

    Research output: Contribution to journalArticle

    30 Citations (Scopus)

    Abstract

    Fatty acids stimulate lipid accumulation in parallel with increased expression of adipose differentiation-related protein (ADRP) in liver cells. Although it is generally considered that the fatty acid effect on ADRP expression is mediated by peroxisome proliferator-activated receptors (PPARs), we identified here an additional molecular mechanism using the NMuLi mouse liver nonparenchymal cell line, which expresses PPARγ and δ but not α. Oleic acid (OA) and specific ligands for PPARγ and -δ stimulated ADRP expression as well as the -2,090-bp ADRP promoter activity which encompasses the PPAR response element (PPRE) adjacent to an Ets/activator protein (AP)-1 site. When the AP-1 site was mutated, OA failed to stimulate the activity despite the presence of the PPRE, whereas ligands for PPARγ and -δ did stimulate it and so did a PPARα ligand under the coexpression of PPARα. DNA binding of AP-1 was stimulated by OA but not by PPAR ligands. Because we previously demonstrated that Pycnogenol (PYC), a French maritime pine bark extract, suppressed ADRP expression in macrophages partly by suppression of AP-1 activity, we tested the effect of PYC on NMuLi cells. PYC reduced the OA-induced ADRP expression along with suppression of lipid droplet formation. However, PYC neither suppressed the OA-stimulated ADRP promoter activity nor DNA binding of AP-1 but, instead, reduced the ADRP mRNA half-life. All these results indicate that the effect of OA on ADRP expression requires AP-1 as well as PPRE, and PYC suppresses the ADRP expression in part by facilitating mRNA degradation. PYC, a widely used dietary supplement, could be beneficial for the prevention of excessive lipid accumulation such as hepatic steatosis.

    Original languageEnglish
    Pages (from-to)E112-E123
    JournalAmerican Journal of Physiology - Endocrinology and Metabolism
    Volume297
    Issue number1
    DOIs
    Publication statusPublished - Jul 1 2009

    Fingerprint

    Peroxisome Proliferator-Activated Receptors
    Transcription Factor AP-1
    RNA Stability
    Response Elements
    Oleic Acid
    Liver
    Ligands
    DNA-Binding Proteins
    Fatty Acids
    pycnogenols
    Perilipin-2
    Lipids
    Pinus
    Dietary Supplements
    Half-Life
    Macrophages
    Cell Line
    Messenger RNA

    All Science Journal Classification (ASJC) codes

    • Endocrinology, Diabetes and Metabolism
    • Physiology
    • Physiology (medical)

    Cite this

    Oleic acid-induced ADRP expression requires both AP-1 and PPAR response elements, and is reduced by Pycnogenol through mRNA degradation in NMuLi liver cells. / Fan, Bin; Ikuyama, Shoichiro; Gu, Jian Qiu; Wei, Ping; Oyama, Jun Ichi; Inoguchi, Toyoshi; Nishimura, Junji.

    In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 297, No. 1, 01.07.2009, p. E112-E123.

    Research output: Contribution to journalArticle

    Fan, Bin ; Ikuyama, Shoichiro ; Gu, Jian Qiu ; Wei, Ping ; Oyama, Jun Ichi ; Inoguchi, Toyoshi ; Nishimura, Junji. / Oleic acid-induced ADRP expression requires both AP-1 and PPAR response elements, and is reduced by Pycnogenol through mRNA degradation in NMuLi liver cells. In: American Journal of Physiology - Endocrinology and Metabolism. 2009 ; Vol. 297, No. 1. pp. E112-E123.
    @article{8411794dc2554eaf9b036cbec87764bc,
    title = "Oleic acid-induced ADRP expression requires both AP-1 and PPAR response elements, and is reduced by Pycnogenol through mRNA degradation in NMuLi liver cells",
    abstract = "Fatty acids stimulate lipid accumulation in parallel with increased expression of adipose differentiation-related protein (ADRP) in liver cells. Although it is generally considered that the fatty acid effect on ADRP expression is mediated by peroxisome proliferator-activated receptors (PPARs), we identified here an additional molecular mechanism using the NMuLi mouse liver nonparenchymal cell line, which expresses PPARγ and δ but not α. Oleic acid (OA) and specific ligands for PPARγ and -δ stimulated ADRP expression as well as the -2,090-bp ADRP promoter activity which encompasses the PPAR response element (PPRE) adjacent to an Ets/activator protein (AP)-1 site. When the AP-1 site was mutated, OA failed to stimulate the activity despite the presence of the PPRE, whereas ligands for PPARγ and -δ did stimulate it and so did a PPARα ligand under the coexpression of PPARα. DNA binding of AP-1 was stimulated by OA but not by PPAR ligands. Because we previously demonstrated that Pycnogenol (PYC), a French maritime pine bark extract, suppressed ADRP expression in macrophages partly by suppression of AP-1 activity, we tested the effect of PYC on NMuLi cells. PYC reduced the OA-induced ADRP expression along with suppression of lipid droplet formation. However, PYC neither suppressed the OA-stimulated ADRP promoter activity nor DNA binding of AP-1 but, instead, reduced the ADRP mRNA half-life. All these results indicate that the effect of OA on ADRP expression requires AP-1 as well as PPRE, and PYC suppresses the ADRP expression in part by facilitating mRNA degradation. PYC, a widely used dietary supplement, could be beneficial for the prevention of excessive lipid accumulation such as hepatic steatosis.",
    author = "Bin Fan and Shoichiro Ikuyama and Gu, {Jian Qiu} and Ping Wei and Oyama, {Jun Ichi} and Toyoshi Inoguchi and Junji Nishimura",
    year = "2009",
    month = "7",
    day = "1",
    doi = "10.1152/ajpendo.00119.2009",
    language = "English",
    volume = "297",
    pages = "E112--E123",
    journal = "American Journal of Physiology - Heart and Circulatory Physiology",
    issn = "0363-6135",
    publisher = "American Physiological Society",
    number = "1",

    }

    TY - JOUR

    T1 - Oleic acid-induced ADRP expression requires both AP-1 and PPAR response elements, and is reduced by Pycnogenol through mRNA degradation in NMuLi liver cells

    AU - Fan, Bin

    AU - Ikuyama, Shoichiro

    AU - Gu, Jian Qiu

    AU - Wei, Ping

    AU - Oyama, Jun Ichi

    AU - Inoguchi, Toyoshi

    AU - Nishimura, Junji

    PY - 2009/7/1

    Y1 - 2009/7/1

    N2 - Fatty acids stimulate lipid accumulation in parallel with increased expression of adipose differentiation-related protein (ADRP) in liver cells. Although it is generally considered that the fatty acid effect on ADRP expression is mediated by peroxisome proliferator-activated receptors (PPARs), we identified here an additional molecular mechanism using the NMuLi mouse liver nonparenchymal cell line, which expresses PPARγ and δ but not α. Oleic acid (OA) and specific ligands for PPARγ and -δ stimulated ADRP expression as well as the -2,090-bp ADRP promoter activity which encompasses the PPAR response element (PPRE) adjacent to an Ets/activator protein (AP)-1 site. When the AP-1 site was mutated, OA failed to stimulate the activity despite the presence of the PPRE, whereas ligands for PPARγ and -δ did stimulate it and so did a PPARα ligand under the coexpression of PPARα. DNA binding of AP-1 was stimulated by OA but not by PPAR ligands. Because we previously demonstrated that Pycnogenol (PYC), a French maritime pine bark extract, suppressed ADRP expression in macrophages partly by suppression of AP-1 activity, we tested the effect of PYC on NMuLi cells. PYC reduced the OA-induced ADRP expression along with suppression of lipid droplet formation. However, PYC neither suppressed the OA-stimulated ADRP promoter activity nor DNA binding of AP-1 but, instead, reduced the ADRP mRNA half-life. All these results indicate that the effect of OA on ADRP expression requires AP-1 as well as PPRE, and PYC suppresses the ADRP expression in part by facilitating mRNA degradation. PYC, a widely used dietary supplement, could be beneficial for the prevention of excessive lipid accumulation such as hepatic steatosis.

    AB - Fatty acids stimulate lipid accumulation in parallel with increased expression of adipose differentiation-related protein (ADRP) in liver cells. Although it is generally considered that the fatty acid effect on ADRP expression is mediated by peroxisome proliferator-activated receptors (PPARs), we identified here an additional molecular mechanism using the NMuLi mouse liver nonparenchymal cell line, which expresses PPARγ and δ but not α. Oleic acid (OA) and specific ligands for PPARγ and -δ stimulated ADRP expression as well as the -2,090-bp ADRP promoter activity which encompasses the PPAR response element (PPRE) adjacent to an Ets/activator protein (AP)-1 site. When the AP-1 site was mutated, OA failed to stimulate the activity despite the presence of the PPRE, whereas ligands for PPARγ and -δ did stimulate it and so did a PPARα ligand under the coexpression of PPARα. DNA binding of AP-1 was stimulated by OA but not by PPAR ligands. Because we previously demonstrated that Pycnogenol (PYC), a French maritime pine bark extract, suppressed ADRP expression in macrophages partly by suppression of AP-1 activity, we tested the effect of PYC on NMuLi cells. PYC reduced the OA-induced ADRP expression along with suppression of lipid droplet formation. However, PYC neither suppressed the OA-stimulated ADRP promoter activity nor DNA binding of AP-1 but, instead, reduced the ADRP mRNA half-life. All these results indicate that the effect of OA on ADRP expression requires AP-1 as well as PPRE, and PYC suppresses the ADRP expression in part by facilitating mRNA degradation. PYC, a widely used dietary supplement, could be beneficial for the prevention of excessive lipid accumulation such as hepatic steatosis.

    UR - http://www.scopus.com/inward/record.url?scp=67650083112&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=67650083112&partnerID=8YFLogxK

    U2 - 10.1152/ajpendo.00119.2009

    DO - 10.1152/ajpendo.00119.2009

    M3 - Article

    C2 - 19383873

    AN - SCOPUS:67650083112

    VL - 297

    SP - E112-E123

    JO - American Journal of Physiology - Heart and Circulatory Physiology

    JF - American Journal of Physiology - Heart and Circulatory Physiology

    SN - 0363-6135

    IS - 1

    ER -