Mast cells function as an alternative modulator of adipogenesis through 15-deoxy-delta-12, 14-prostaglandin J2
Mast cells function as an alternative modulator of adipogenesis through 15-deoxy-delta-12, 14-prostaglandin J2
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DOI：
10.1152/ajpcell.00514.2010
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发表时间：
2011-12-01
影响因子：
5.5
通讯作者：
Matsuda, Hiroshi
中科院分区：
文献类型：
--
作者：
Tanaka, Akane;Nomura, Yoshihiro;Matsuda, Hiroshi
吴文龙，张晓刚.肥大细胞通过15-脱氧-δ-12，14-前列腺素J作为脂肪生成的替代调节剂发挥作用（2）。美国生理学杂志细胞生理学301：C1360-C1367，2011年。首次发表于2011年8月24日; doi：10.1152/ajpcell.00514.2010.-肥大细胞是前列腺素的主要生产者之一。PGs 15-脱氧-δ-12，14-PGJ（2）（15-脱氧-δ PGJ（2））的最终代谢产物是过氧化物酶体增殖物激活受体（PPAR）γ的内源性配体。PPAR γ调节脂肪细胞分化，因此，我们试图研究是否来自肥大细胞的前列腺素对脂肪形成的影响。我们发现在高脂饮食喂养的肥胖小鼠的脂肪组织中肥大细胞数量的增加使我们能够推测肥大细胞对脂肪形成的贡献。通过使用3 T3 L1细胞评价肥大细胞介导的脂肪形成诱导。从用钙离子载体刺激或高糖条件刺激的肥大细胞获得的上清液含有15-脱氧-δ PGJ（2），并诱导3 T3 L1细胞的脂肪形成。来自上清液的PGJ 2对PPAR γ的激动活性通过报告基因测定来证实。从钙离子载体刺激的骨髓来源的培养的肥大细胞（BMCMC）收集的培养液激活NIH 3 T3成纤维细胞中的PPAR-responsive元件，并且PPAR-gamma的特异性抑制剂取消激活。肥大细胞对肥胖的贡献是通过使用肥大细胞缺陷小鼠饲喂西方饮食来评估的。与同窝野生型小鼠相比，肥大细胞缺陷小鼠在高脂喂养期间的体重增加受损;另一方面，骨髓来源的培养肥大细胞移植到肥大细胞缺陷小鼠中，通过摄入高脂饮食恢复了体重增加。在这项研究中，我们清楚地表明，肥大细胞产生PG在响应高葡萄糖条件和诱导脂肪细胞分化，并可能肥胖。这是第一个研究，提供了一个新的作用，肥大细胞通过激活过氧化物酶体增殖物激活受体γ脂肪形成的证据。
Tanaka A, Nomura Y, Matsuda A, Ohmori K, Matsuda H. Mast cells function as an alternative modulator of adipogenesis through 15-deoxy-delta-12,14-prostaglandin J(2). Am J Physiol Cell Physiol 301: C1360-C1367, 2011. First published August 24, 2011; doi:10.1152/ajpcell.00514.2010.-Mast cells are one of the major producers of prostaglandins (PGs). The final metabolite of PGs 15-deoxy-delta-12,14-PGJ(2) (15-deoxy-delta PGJ(2)) is the endogenous ligand of the peroxisome proliferator-activated receptor (PPAR) gamma. PPAR gamma modulates adipocyte differentiation; therefore, we attempted to investigate whether PGs derived from mast cells influenced on adipogenesis. We found the increase of mast cell numbers in fat tissue of obese mice fed with a high-fat diet allowed us to speculate contributions of mast cells to adipogenesis. Mast cell-mediated induction of adipogenesis was evaluated by using 3T3 L1 cells. Supernatants obtained from mast cells stimulated with calcium ionophore or the high-glucose condition contained 15-deoxy-delta PGJ(2) and induced adipogenesis of 3T3 L1 cells. Agonistic activity of PGJ2 from the supernatants on PPAR gamma was confirmed by a reporter gene assay. Culture medium collected from calcium ionophore-stimulated bone marrow-derived cultured mast cells (BMCMC) activated PPAR-responsive element in NIH3T3 fibroblasts, and the specific inhibitor of PPAR gamma canceled the activation. Contribution of mast cells to obesity was evaluated by using mast cell-deficient mice fed with a Western diet. Weight gain of mast cell-deficient mice during high-fat feeding was impaired compared with their littermate wild-type mice; on the other hand, transplantation of bone marrow-derived cultured mast cells to mast cell-deficient mice restored the weight gain by intake of a high-fat diet. In this study, we clearly demonstrated that mast cells produced PGs in response to the high-glucose condition and induced adipocyte differentiation and possibly obesity. This is the first study that provides evidence for a novel role of mast cells in adipogenesis via PPAR gamma activation.