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Papers In Press, published online ahead of print November 4, 2002
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Submitted on August 29, 2002
Revised on October 28, 2002
Accepted on November 1, 2002
Departmente de Biochimie, CNRS, UMR 6543, Nice 06108
Corresponding Author: ailhaud{at}unice.fr
The increasing prevalence of childhood obesity results from a combination of environmental factors. Among them, high-fat intake is associated with fat mass gain through fatty acid activation of peroxisome proliferator-activated receptors delta and gamma which promote adipogenesis. We now show that, compared to a combination of specific agonists to both receptors or to saturated, monounsaturated and omega-3 polyunsaturated fatty acids. (eicosapentaenoic and docosahexaenoic acids), arachidonic acid (C20:4, omega-6) is substantially more adipogenic in promoting the differentiation of clonal preadipocytes. This effect takes place at an early stage in the process, is blocked by cyclooxygenase inhibitors and is mimicked by carbacyclin, suggesting a role for the prostacyclin receptor (IP-R) and activation of the cyclic AMP-dependent pathways which are known to regulate the expression of the CCAAT enhancer binding proteins beta and delta implicated in adipogenesis. In vivo, 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 also enriched in linoleic acid and alpha-linolenic acid, a precursor of eicosapentaenoic and docosahexaenoic acids (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 LO diet or LO/LL diet were similar in this respect, indicating that the prostacyclin receptor is crucial in adipose tissue development. As polyunsaturated fatty acids are not equipotent in enhancing fat mass, this raises the issue of the high content of linoleic acid of the lipids ingested by women during pregnancy and lactation. It raises also the issue of its large supplementation in formula milk and infant foods, and the possible relationship with the epidemic of childhood obesity.
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