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

doi: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

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

Research output: Contribution to journal › Article › peer-review

32 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 language	English
Pages (from-to)	4743-4748
Number of pages	6
Journal	FEBS Letters
Volume	581
Issue number	24
DOIs	https://doi.org/10.1016/j.febslet.2007.08.072
Publication status	Published - 2007

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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10.1016/j.febslet.2007.08.072

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title = "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",

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",

author = "Nikolaos Dimopoulos and Maria Watson and Charlotte Green and Hundal, \{Harinder S\}",

year = "2007",

doi = "10.1016/j.febslet.2007.08.072",

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volume = "581",

pages = "4743--4748",

journal = "FEBS Letters",

issn = "0014-5793",

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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

PY - 2007

Y1 - 2007

N2 - 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.

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.

KW - Animals

KW - Carnitine O-Palmitoyltransferase

KW - Cell Line

KW - Fatty Acids

KW - Glucose

KW - Glycogen

KW - Insulin

KW - Muscle Fibers, Skeletal

KW - Muscle, Skeletal

KW - Oxidation-Reduction

KW - PPAR delta

KW - RNA-Binding Proteins

KW - Rats

KW - Sensitivity and Specificity

KW - Thiazoles

KW - Transcription Factors

U2 - 10.1016/j.febslet.2007.08.072

DO - 10.1016/j.febslet.2007.08.072

M3 - Article

C2 - 17869249

SN - 0014-5793

VL - 581

SP - 4743

EP - 4748

JO - FEBS Letters

JF - FEBS Letters

IS - 24

ER -

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

Abstract

Keywords

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