Arachidonic acid and prostacyclin signaling promote adipose tissue development: a human health concern?

作者：Florence Massiéra, Perla Saint-Marc, Josiane Seydoux, Tatsunori Murata, Takuya Kobayashi, Shuh Narumiya, Philippe Guesnet, Ez‐Zoubir Amri, Raymond Négrel, Gerard P. Ailhaud · 发表于：Journal of Lipid Research · 年份：2003 · DOI：10.1194/jlr.m200346-jlr200 · 被引用次数：296 · 研究领域：Peroxisome Proliferator-Activated Receptors、Fatty Acid Research and Health、Adipose Tissue and Metabolism

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 show herein that, compared to a combination of specific agonists to both receptors or to saturated, monounsaturated, and omega-3 polyunsaturated fatty acids, arachidonic acid (C20:4, omega-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 beta and delta 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 alpha-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 chil...