Involvement of guanylin and GC-C in rat mesenteric macrophages in resistance to a high-fat diet
Involvement of guanylin and GC-C in rat mesenteric macrophages in resistance to a high-fat diet
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DOI：
10.1194/jlr.m029017
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发表时间：
2013-01-01
影响因子：
6.5
通讯作者：
Date, Yukari
中科院分区：
文献类型：
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作者：
Akieda-Asai, Sayaka;Sugiyama, Masako;Date, Yukari
高脂饮食（HFD）是一个众所周知的促进肥胖发展的因素。大多数喂食HFD的大鼠变得肥胖。那些在喂食HFD时避免肥胖的人被认为是饮食抵抗（DR）。我们进行了微阵列筛选，以确定特定的基因，以肠系膜脂肪的DR大鼠，并揭示了高表达的鸟苷素和鸟苷酸环化酶C（GC-C）在一些科目。我们的组织学研究表明鸟苷素和GC-C的细胞来源是巨噬细胞。因此，我们开发了在巨噬细胞中过表达鸟苷素和GC-C的双转基因（Tg）大鼠，并发现它们对HFD的作用具有抗性。在HFD喂养的Tg大鼠的肠系膜脂肪中，Fas和perilipin mRNA下调，与HFD喂养的野生型大鼠的水平相比，参与脂肪酸氧化的基因上调。体外研究表明，在与表达鸟苷素和GC-C的巨噬细胞共培养的脂肪细胞中，脂质积累被显著抑制，并且在用鸟苷素和GC-C特异性siRNA处理后，这种抑制作用降低。我们的研究结果表明，巨噬细胞鸟苷脂-GC-C系统有助于改变参与脂质代谢的基因表达，从而抵抗肥胖。Akieda-Asai，S.，M. Sugiyama，T. Miyazawa，S.科达岛Okano，K. Senba，P.- E. Poleni，Y. Hizukuri，A.冈本托K. Yamahara，E. Mutoh，F. Aoyama，A. Sawaguchi，M. Furuya，M. Miyazato，K. Kangawa和Y.约会鸟苷素和GC-C参与大鼠肠系膜巨噬细胞对高脂饮食的抵抗。J. Lipid Res. 54：85-96。
A high-fat diet (HFD) is a well-known contributing factor in the development of obesity. Most rats fed HFDs become obese. Those that avoid obesity when fed HFDs are considered diet resistant (DR). We performed a microarray screen to identify genes specific to the mesenteric fat of DR rats and revealed high expression of guanylin and guanylyl cyclase C (GC-C) in some subjects. Our histologic studies revealed that the cellular source of guanylin and GC-C is macrophages. Therefore, we developed double- transgenic (Tg) rats overexpressing guanylin and GC-C in macrophages and found that they were resistant to the effects of HFDs. In the mesenteric fat of HFD-fed Tg rats, Fas and perilipin mRNAs were downregulated, and those of genes involved in fatty acid oxidation were upregulated, compared with the levels in HFD-fed wild-type rats. In vitro studies demonstrated that lipid accumulation was markedly inhibited in adipocytes cocultured with macrophages expressing guanylin and GC-C and that this inhibition was reduced after treatment with guanylin-and GC-C-specific siRNAs. Our results suggest that the macrophagic guanylin-GC-C system contributes to the altered expression of genes involved in lipid metabolism, leading to resistance to obesity.-Akieda-Asai, S., M. Sugiyama, T. Miyazawa, S. Koda, I. Okano, K. Senba, P.-E. Poleni, Y. Hizukuri, A. Okamoto, K. Yamahara, E. Mutoh, F. Aoyama, A. Sawaguchi, M. Furuya, M. Miyazato, K. Kangawa, and Y. Date. Involvement of guanylin and GC-C in rat mesenteric macrophages in resistance to a high-fat diet. J. Lipid Res. 54: 85-96.