The PPARdelta agonist, GW501516, promotes fatty acid oxidation but has no direct effect on glucose utilisation or insulin sensitivity in rat L6 skeletal muscle cells

Nikolaos Dimopoulos, Maria Watson, Charlotte Green, Harinder S Hundal

    Research output: Contribution to journal › Article

    26 Citations (Scopus)

    Abstract

    Peroxisome proliferator-activated receptor-delta (PPARdelta) activation enhances skeletal muscle fatty acid oxidation and improves whole body glucose homeostasis and insulin sensitivity. Recently, GW501516, a selective PPARdelta agonist, was reported to increase glucose uptake in human skeletal myotubes by an AMPK-dependent mechanism that may contribute to the improved glucose tolerance. Here, we demonstrate that whilst GW501516 increases expression of PGC-1alpha and CPT-1 and stimulates fatty-acid oxidation in L6 myotubes, it fails to enhance insulin sensitivity, AMPK activity or glucose uptake and storage. Our findings exclude sarcolemmal glucose transport as a potential target for the therapeutic action of PPARdelta agonists in skeletal muscle.
    Original languageEnglish
    Pages (from-to)4743-4748
    Number of pages6
    JournalFEBS Letters
    Volume581
    Issue number24
    DOIs
    Publication statusPublished - 2007

    Fingerprint

    PPAR delta
    Muscle Cells
    Muscle
    Insulin Resistance
    Rats
    Skeletal Muscle
    Fatty Acids
    Cells
    Insulin
    Glucose
    Oxidation
    AMP-Activated Protein Kinases
    Skeletal Muscle Fibers
    Homeostasis
    Chemical activation
    GW 501516

    Keywords

    • Animals
    • Carnitine O-Palmitoyltransferase
    • Cell Line
    • Fatty Acids
    • Glucose
    • Glycogen
    • Insulin
    • Muscle Fibers, Skeletal
    • Muscle, Skeletal
    • Oxidation-Reduction
    • PPAR delta
    • RNA-Binding Proteins
    • Rats
    • Sensitivity and Specificity
    • Thiazoles
    • Transcription Factors

    Cite this

    Dimopoulos, Nikolaos ; Watson, Maria ; Green, Charlotte ; Hundal, Harinder S. / The PPARdelta agonist, GW501516, promotes fatty acid oxidation but has no direct effect on glucose utilisation or insulin sensitivity in rat L6 skeletal muscle cells. In: FEBS Letters. 2007 ; Vol. 581, No. 24. pp. 4743-4748.
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    abstract = "Peroxisome proliferator-activated receptor-delta (PPARdelta) activation enhances skeletal muscle fatty acid oxidation and improves whole body glucose homeostasis and insulin sensitivity. Recently, GW501516, a selective PPARdelta agonist, was reported to increase glucose uptake in human skeletal myotubes by an AMPK-dependent mechanism that may contribute to the improved glucose tolerance. Here, we demonstrate that whilst GW501516 increases expression of PGC-1alpha and CPT-1 and stimulates fatty-acid oxidation in L6 myotubes, it fails to enhance insulin sensitivity, AMPK activity or glucose uptake and storage. Our findings exclude sarcolemmal glucose transport as a potential target for the therapeutic action of PPARdelta agonists in skeletal muscle.",
    keywords = "Animals, Carnitine O-Palmitoyltransferase, Cell Line, Fatty Acids, Glucose, Glycogen, Insulin, Muscle Fibers, Skeletal, Muscle, Skeletal, Oxidation-Reduction, PPAR delta, RNA-Binding Proteins, Rats, Sensitivity and Specificity, Thiazoles, Transcription Factors",
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    Dimopoulos, N, Watson, M, Green, C & Hundal, HS 2007, 'The PPARdelta agonist, GW501516, promotes fatty acid oxidation but has no direct effect on glucose utilisation or insulin sensitivity in rat L6 skeletal muscle cells', FEBS Letters, vol. 581, no. 24, pp. 4743-4748. https://doi.org/10.1016/j.febslet.2007.08.072

    The PPARdelta agonist, GW501516, promotes fatty acid oxidation but has no direct effect on glucose utilisation or insulin sensitivity in rat L6 skeletal muscle cells. / Dimopoulos, Nikolaos; Watson, Maria; Green, Charlotte; Hundal, Harinder S.

    In: FEBS Letters, Vol. 581, No. 24, 2007, p. 4743-4748.

    Research output: Contribution to journal › Article

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    T1 - The PPARdelta agonist, GW501516, promotes fatty acid oxidation but has no direct effect on glucose utilisation or insulin sensitivity in rat L6 skeletal muscle cells

    AU - Dimopoulos, Nikolaos

    AU - Watson, Maria

    AU - Green, Charlotte

    AU - Hundal, Harinder S

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    AB - Peroxisome proliferator-activated receptor-delta (PPARdelta) activation enhances skeletal muscle fatty acid oxidation and improves whole body glucose homeostasis and insulin sensitivity. Recently, GW501516, a selective PPARdelta agonist, was reported to increase glucose uptake in human skeletal myotubes by an AMPK-dependent mechanism that may contribute to the improved glucose tolerance. Here, we demonstrate that whilst GW501516 increases expression of PGC-1alpha and CPT-1 and stimulates fatty-acid oxidation in L6 myotubes, it fails to enhance insulin sensitivity, AMPK activity or glucose uptake and storage. Our findings exclude sarcolemmal glucose transport as a potential target for the therapeutic action of PPARdelta agonists in skeletal muscle.

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    KW - Carnitine O-Palmitoyltransferase

    KW - Cell Line

    KW - Fatty Acids

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    KW - Glycogen

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    KW - Oxidation-Reduction

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    KW - RNA-Binding Proteins

    KW - Rats

    KW - Sensitivity and Specificity

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    Dimopoulos N, Watson M, Green C, Hundal HS. The PPARdelta agonist, GW501516, promotes fatty acid oxidation but has no direct effect on glucose utilisation or insulin sensitivity in rat L6 skeletal muscle cells. FEBS Letters. 2007;581(24):4743-4748. https://doi.org/10.1016/j.febslet.2007.08.072

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