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

By Rodolphe Dusaulcy, Chloé Rancoule, Sandra Grès, Estelle Wanecq, André Colom, Charlotte Guigné, Laurens A. van Meeteren, Wouter H. Moolenaar, Philippe Valet and Jean Sébastien Saulnier-Blache

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 ATXF/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

Topics: Research Articles
Publisher: The American Society for Biochemistry and Molecular Biology
OAI identifier: oai:pubmedcentral.nih.gov:3090245
Provided by: PubMed Central
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