Massiera Florence, Saint-Marc Perla, Seydoux Josiane, Murata Takahiko, Kobayashi Takuya, Narumiya Shuh, Guesnet Philippe, Amri Ez-Zoubir, Negrel Raymond, Ailhaud Gérard
Institut de Recherche Signalisation, Biologie du Développement et Cancer, Centre de Biochimie (UMR6543CNRS), UNSA, Faculté des Sciences, Parc Valrose, 06108 Nice cedex 2, France.
J Lipid Res. 2003 Feb;44(2):271-9. doi: 10.1194/jlr.M200346-JLR200. Epub 2002 Nov 4.
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 childhood obesity.
高脂肪摄入通过过氧化物酶体增殖物激活受体δ和γ的脂肪酸激活与脂肪量增加相关，而过氧化物酶体增殖物激活受体δ和γ可促进脂肪生成。我们在此表明，与两种受体的特异性激动剂组合或与饱和脂肪酸、单不饱和脂肪酸和ω-3多不饱和脂肪酸相比，花生四烯酸（C20:4，ω-6）可显著促进克隆前脂肪细胞的分化。这种作用被环氧化酶抑制剂阻断，并被卡前列环素模拟，这表明前列环素受体起作用以及环磷酸腺苷依赖性途径被激活，该途径调节与脂肪生成相关的CCAAT增强子结合蛋白β和δ的表达。在怀孕-哺乳期，给母鼠喂食富含花生四烯酸前体亚油酸的高脂肪饮食（LO饮食），或富含亚油酸和α-亚麻酸的相同热量饮食（LO/LL饮食）。从断奶开始的体重、脂肪量、附睾脂肪垫重量以及8周龄时的脂肪细胞大小，LO饮食组均高于LO/LL饮食组。相比之下，无论喂食哪种饮食，前列环素受体缺陷小鼠在这方面都相似，这表明前列环素信号传导有助于脂肪组织发育。这些结果引发了关于以下两个方面亚油酸高含量的问题：i）怀孕和哺乳期摄入的脂质，以及ii）与儿童肥胖流行相关的配方奶和婴儿食品。
