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Toll-like receptor signalling induced by endurance exercise

Publication: Applied Physiology, Nutrition, and Metabolism
12 May 2009


Toll-like receptors (TLRs) are transmembrane proteins that detect a variety of molecular components mostly derived from microorganisms. TLR2 and TLR4 are amongst others present in liver, adipose tissue, and skeletal muscle. Extracellular long-chain fatty acids bind TLR2 and 4 and induce downstream signalling cascades implicated in cellular stress and inflammatory processes. Evidence indicates that TLR activation by non-esterified fatty acids (NEFAs) may participate in the development of insulin resistance. Exercise seems to induce a downregulation of TLR expression in various tissues, a mechanism that may take part in the protective effect of exercise against insulin resistance. Moreover, TLRs seem to mediate the activation of mitogen-activated protein kinase p38 and Jun-amino-terminal kinase by extracellular NEFAs during endurance exercise. During this type of exercise, circulating NEFAs are known to regulate the expression of various genes including pyruvate dehydrogenase kinase 4, uncoupling protein 3, carnitine palmitoyltransferase 1, and peroxisome proliferator-activated receptor-gamma coactivator 1 alpha. Whether these events are initiated by a TLR-dependent signal transduction remains to be investigated.


Les récepteurs Toll-like (TLR) sont des protéines transmembranaires qui détectent un certain nombre de composants moléculaires principalement dérivés des microorganismes. TLR2 et TLR4 sont entre autres présents dans le foie, le tissu adipeux et le muscle squelettique. Les acides gras à longues chaines extracellulaires lient TLR2 et TLR4 et activent en aval des cascades de signalisation impliquées dans le stress cellulaire et dans les mécanismes inflammatoires. D’après des données probantes, l’activation des TLR par les acides gras non estérifiés (NEFA) jouerait un rôle dans le développement de l’insulinorésistance. L’exercice susciterait une régulation à la baisse de l’expression des TLR dans divers tissus. Ce phénomène pourrait constituer un mécanisme de protection de l’exercice physique contre l’insulinorésitance. De plus, au cours d’un exercice d’endurance, les TLR participeraient à l’activation des MAPK (protéines kinases activées par des agents mitogènes) p38 et JNK (« jun-amino-terminal kinase ») par les NEFA extracellulaires. Durant ce genre d’effort, les NEFA circulant contrôlent, on le sait, l’expression de divers gènes dont celui de la pyruvate déshydrogenase kinase 4 (PDK4), de la protéine découplante 3 (UCP3), de la carnitine palmitoyltransférase 1 (CPT-1) et du co-activateur-1α du récepteur γ au facteur activé de prolifération des peroxysomes (PGC1-α). Il reste à établir si ces événements sont initiés par un signal de transduction issu des TLR.

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Published In

cover image Applied Physiology, Nutrition, and Metabolism
Applied Physiology, Nutrition, and Metabolism
Volume 34Number 3June 2009
Pages: 454 - 458


Received: 3 March 2009
Accepted: 3 March 2009
Version of record online: 12 May 2009


This paper is one of a selection of papers published in this Special Issue, entitled 14th International Biochemistry of Exercise Conference – Muscles as Molecular and Metabolic Machines, and has undergone the Journal’s usual peer review process.


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Key Words

  1. fatty acids
  2. MAPK
  3. NFκB
  4. LPS
  5. skeletal muscle
  6. cytokines
  7. TLR2
  8. TLR4
  9. insulin resistance
  10. diabetes


  1. acides gras
  2. MAPK
  3. NF-κB
  4. LPS
  5. muscle squelettique
  6. cytokine
  7. TLR2
  8. TLR4
  9. insulinorésistance
  10. diabète



Research Group in Muscle and Exercise Physiology, Institute of Neuroscience, Université catholique de Louvain, Place Pierre de Coubertin – 1, 1348 Louvain-la-Neuve, Belgium (e-mail: (email: [email protected])).

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