Adipose-specific disruption of autotaxin enhances nutritional fattening and reduces plasma lysophosphatidic acid.

Abstract : Autotaxin (ATX) is a secreted lysophospholipase D that generates the lipid mediator lysophosphatidic acid (LPA). ATX is secreted by adipose tissue and its expression is enhanced in obese/insulin-resistant individuals. Here, we analyzed the specific contribution of adipose-ATX to fat expansion associated with nutritional obesity and its consequences on plasma LPA levels. We established ATX(F/F)/aP2-Cre (FATX-KO) transgenic mice carrying a null ATX allele specifically in adipose tissue. FATX-KO mice and their control littermates were fed either a normal or a high-fat diet (HFD) (45% fat) for 13 weeks. FATX-KO mice showed a strong decrease (up to 90%) in ATX expression in white and brown adipose tissue, but not in other ATX-expressing organs. This was associated with a 38% reduction in plasma LPA levels. When fed an HFD, FATX-KO mice showed a higher fat mass and a higher adipocyte size than control mice although food intake was unchanged. This was associated with increased expression of peroxisome proliferator-activated receptor (PPAR)γ2 and of PPAR-sensitive genes (aP2, adiponectin, leptin, glut-1) in subcutaneous white adipose tissue, as well as in an increased tolerance to glucose. These results show that adipose-ATX is a negative regulator of fat mass expansion in response to an HFD and contributes to plasma LPA levels.
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Journal of Lipid Research, American Society for Biochemistry and Molecular Biology, 2011, 52 (6), pp.1247-55. 〈10.1194/jlr.M014985〉
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Soumis le : lundi 29 août 2011 - 16:34:18
Dernière modification le : jeudi 1 septembre 2011 - 11:21:49

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Rodolphe Dusaulcy, Chloé Rancoule, Sandra Grès, Estelle Wanecq, André Colom, et al.. Adipose-specific disruption of autotaxin enhances nutritional fattening and reduces plasma lysophosphatidic acid.. Journal of Lipid Research, American Society for Biochemistry and Molecular Biology, 2011, 52 (6), pp.1247-55. 〈10.1194/jlr.M014985〉. 〈inserm-00617583〉

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