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L’acide lysophosphatidique: un lien entre obésité et intolérance au glucose

Lysophosphatidic acid: a link between obesity and glucose-intolerance

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Obésité

Résumé

L’acide lysophosphatidique (LPA) est un médiateur lipidique agissant via des récepteurs spécifiques (LPAR) et est synthétisé par l’autotaxine (ATX), une lysophospholipase D sécrétée. L’expression de l’ATX augmente chez l’obèse intolérant au glucose. Le LPA inhibe l’adipogenèse et réduit la tolérance au glucose par inhibition de la sécrétion d’insuline. Chez des souris obèses suite à un régime hyperlipidique, l’invalidation de l’ATX dans les adipocytes (FATXKO) ou le traitement par un antagoniste des LPAR amplifient l’expansion de la masse grasse tout en améliorant la tolérance au glucose et à l’insuline. L’ATX et les LPARs représentent des cibles pharmacologiques d’intérêt dans le traitement des atteintes métaboliques associées à l’obésité.

Abstract

Lysophosphatidicacid (LPA) is a lipid mediator acting through specific receptors (LPAR) and is synthesized by autotaxin (ATX), a secreted lysophospholipase D. ATX expression is increased in gluco-intolerant obese individuals. LPA inhibits adipogenesis and impairs glucose tolerance through inhibition of insulin secretion. In obesemice fed a high fat diet, invalidation ATX in adipocytes (FATX-KOmice), or treatment with a LPAR antagonist, enhance adipose tissue expansion while improving glucose and insulin tolerance. Thus, ATX and LPAR represent potential pharmacological targets to treat obesity-associated metabolic diseases.

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Authors and Affiliations

  1. Institut des maladies métaboliques et cardiovasculaires (I2MC), Inserm U1048, Université Paul Sabatier, Toulouse, France

    C. Rancoule, R. Dusaulcy, K. Tréguer, S. Grès & J. -S. Saulnier-Blache

  2. Montreal Diabetes Research Center and CRCHUM, Montreal, QC, Canada

    C. Attané

  3. Institut des maladies métaboliques et cardiovasculaires (I2MC), Inserm U1048, 1, avenue Jean Poulhès, BP 84225, 31432, Toulouse cedex 4, France

    C. Attané

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  1. C. Rancoule
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  2. R. Dusaulcy
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  3. C. Attané
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  4. K. Tréguer
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  5. S. Grès
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  6. J. -S. Saulnier-Blache
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Correspondence to J. -S. Saulnier-Blache.

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Rancoule, C., Dusaulcy, R., Attané, C. et al. L’acide lysophosphatidique: un lien entre obésité et intolérance au glucose. Obes 8, 244–247 (2013). https://doi.org/10.1007/s11690-013-0384-7

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  • DOI: https://doi.org/10.1007/s11690-013-0384-7

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