Activation of PPAR-δ in isolated rat skeletal muscle switches fuel preference from glucose to fatty acids

@article{Brunmair2006ActivationOP,
  title={Activation of PPAR-$\delta$ in isolated rat skeletal muscle switches fuel preference from glucose to fatty acids},
  author={Barbara Brunmair and Katrin Staniek and Jos{\'e} D{\"o}rig and Zsuzsanna Sz{\"o}cs and Karin Stadlbauer and V. Marian and Florian Gras and Christian Heinz Anderwald and Hans Nohl and Werner Waldh{\"a}usl and Clemens F{\"u}rnsinn},
  journal={Diabetologia},
  year={2006},
  volume={49},
  pages={2713-2722}
}
Aims/hypothesisGW501516, an agonist of peroxisome proliferator-activated receptor-δ (PPAR-δ), increases lipid combustion and exerts antidiabetic action in animals, effects which are attributed mainly to direct effects on skeletal muscle. We explored such actions further in isolated rat skeletal muscle.Materials and methodsSpecimens of rat skeletal muscle were pretreated with GW501516 (0.01–30 μmol/l) for 0.5, 4 or 24 h and rates of fuel metabolism were then measured. In addition, effects on… 
Endogenous peroxisome proliferator-activated receptor-gamma augments fatty acid uptake in oxidative muscle.
TLDR
It is demonstrated that PPARgamma, even in the absence of exogenous activators, is required for normal rates of fatty acid uptake in oxidative skeletal muscle via mechanisms independent of AMPK and fatty acid transport protein 1.
Role of AMP Kinase and PPARδ in the Regulation of Lipid and Glucose Metabolism in Human Skeletal Muscle*
TLDR
This study confirmed that incubation of primary cultured human muscle cells with GW501516 induced AMPK phosphorylation and increased fatty acid transport and oxidation and glucose uptake and demonstrated that PPARδ expression is required for the effect of GW 501516 on the intracellular accumulation of fatty acids.
Peroxisome proliferator-activated receptor-δ, a regulator of oxidative capacity, fuel switching and cholesterol transport
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Investigation of this nuclear receptor has greatly improved knowledge of the physiological regulation of whole-body fuel turnover and the interdependence of mitochondrial function and insulin sensitivity.
Mitochondrial Utilization of Competing Fuels Is Altered in Insulin Resistant Skeletal Muscle of Non-obese Rats (Goto-Kakizaki)
TLDR
With competing fuels, the presence of fatty acids diminishes mitochondria ability to utilize carbohydrate derived substrates in insulin-resistant muscle despite reduced PPARδ content.
Oral administration of a PPAR-delta agonist to rodents worsens, not improves, maximal insulin-stimulated glucose transport in skeletal muscle of different fibers.
TLDR
It is proposed that chronic treatment with the PPAR-delta agonist GW 501516 may induce or worsen insulin resistance in rodent skeletal muscle by increasing the capacity for FA transport across the sarcolemma without a sufficient compensatory increase in FA oxidation.
Selective PPARδ agonist treatment increases skeletal muscle lipid metabolism without altering mitochondrial energy coupling: an in vivo magnetic resonance spectroscopy study
TLDR
These are the first noninvasive measurements illustrating a selective PPARdelta-mediated decrease in muscle lipid content that was consistent with a shift in metabolic substrate utilization from carbohydrate to lipid.
Peroxisome Proliferator-Activated Receptor Delta: A Conserved Director of Lipid Homeostasis through Regulation of the Oxidative Capacity of Muscle
TLDR
The main aim of this review is to highlight the central role for activated PPARδ in the reversal of any tendency toward the development of insulin resistance.
PPARδ activation in human myotubes increases mitochondrial fatty acid oxidative capacity and reduces glucose utilization by a switch in substrate preference
TLDR
It is confirmed that the principal effect of PPARδ activation was to increase mitochondrial fatty acid oxidative capacity and reduced glucose utilization through a switch in mitochondrial substrate preference by up-regulating pyruvate dehydrogenase kinase isozyme 4 and genes involved in lipid metabolism and fatty acid oxidation.
Peroxisome Proliferator-Activated Receptor -β/δ, -γ Agonists and Resveratrol Modulate Hypoxia Induced Changes in Nuclear Receptor Activators of Muscle Oxidative Metabolism
TLDR
It is demonstrated that hypoxia alters the components of the PPAR pathway involved in muscle fatty acid oxidative gene transcription and translation and how it might impact long-term muscle oxidative metabolism and insulin sensitivity.
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