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

• Published in: Journal of lipid research 2011-06, Vol.52 (6), p.1247-1255
• Main Authors: Dusaulcy, Rodolphe, Rancoule, Chloé, Grès, Sandra, Wanecq, Estelle, Colom, André, Guigné, Charlotte, van Meeteren, Laurens A., Moolenaar, Wouter H., Valet, Philippe, Saulnier-Blache, Jean Sébastien
• Format: Article
• Language: English
• Subjects: adipocyte; Adipocytes - cytology; Adipocytes - metabolism; Adipose Tissue, Brown - metabolism; Adipose Tissue, Brown - physiopathology; Adipose Tissue, White - metabolism; Adipose Tissue, White - physiopathology; Adiposity; Animals; Blood Glucose - analysis; Cell Size; Dietary Fats - adverse effects; Dietary Fats - metabolism; Disease Models, Animal; Female; Founder Effect; Gene Deletion; Glucose Tolerance Test; high-fat diet; Insulin - blood; Lysophospholipids - blood; Male; Mice; Mice, Knockout; Multienzyme Complexes - deficiency; Multienzyme Complexes - genetics; obesity; Obesity - genetics; Obesity - metabolism; Obesity - physiopathology; Phosphodiesterase I - deficiency; Phosphodiesterase I - genetics; Phosphoric Diester Hydrolases; PPAR gamma - antagonists & inhibitors; PPAR gamma - genetics; PPAR gamma - metabolism; Pyrophosphatases - deficiency; Pyrophosphatases - genetics
• ISSN: 0022-2275; 1539-7262
• DOI: 10.1194/jlr.M014985

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.