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Journal of Lipid Research, Vol. 44, 271-279, February 2003
Copyright © 2003 by Lipid Research, Inc.

Arachidonic acid and prostacyclin signaling promote adipose tissue development

Florence Massiera^*, Perla Saint-Marc^*, Josiane Seydoux, Takahiko Murata, Takuya Kobayashi, Shuh Narumiya, Philippe Guesnet^**, Ez-Zoubir Amri^*, Raymond Negrel^* and Gérard Ailhaud^1,*

^* Institut de Recherche Signalisation, Biologie du Développement et Cancer, Centre de Biochimie (UMR6543CNRS), UNSA, Faculté des Sciences, Parc Valrose, 06108 Nice cedex 2, France
Centre Médical Universitaire, Département de Physiologie, 1 rue Michel Servet, 1211 Genève 4, Switzerland
Department of Pharmacology, Kyoto University, Faculty of Medicine, Yoshida, Sakyo-ku, Kyoto 606-8315, Japan
^** Laboratoire de Nutrition et Sécurité Alimentaire, INRA, 78352 Jouy-en-Josas, France

¹ To whom correspondence should be addressed. e-mail: ailhaud{at}unice.fr

High fat intake is associated with fat mass gain through fatty acid activation of peroxisome proliferator-activated receptors and , which promote adipogenesis. We show herein that, compared to a combination of specific agonists to both receptors or to saturated, monounsaturated, and -3 polyunsaturated fatty acids, arachidonic acid (C20:4, -6) promoted substantially the differentiation of clonal preadipocytes. This effect was blocked by cyclooxygenase inhibitors and mimicked by carbacyclin, suggesting a role for the prostacyclin receptor and activation of the cyclic AMP-dependent pathways that regulate the expression of the CCAAT enhancer binding proteins ß and implicated in adipogenesis. During the pregnancy-lactation period, mother mice were fed either a high-fat diet rich in linoleic acid, a precursor of arachidonic acid (LO diet), or the same isocaloric diet enriched in linoleic acid and -linolenic acid (LO/LL diet). Body weight from weaning onwards, fat mass, epididymal fat pad weight, and adipocyte size at 8 weeks of age were higher with LO diet than with LO/LL diet. In contrast, prostacyclin receptor-deficient mice fed either diet were similar in this respect, indicating that the prostacyclin signaling contributes to adipose tissue development.

These results raise the issue of the high content of linoleic acid of i) ingested lipids during pregnancy and lactation, and ii) formula milk and infant foods in relation to the epidemic of childhood obesity.

Abbreviations: ALBP (aP2), adipocyte lipid binding protein; PKA, protein kinase A

Supplementary key words prostacyclin receptor-deficient mice • adipogenesis • pregnancy-lactation • childhood obesity

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