Eicosapentaenoic Acid and Rosiglitazone Increase Adiponectin in an Additive and PPARγ-Dependent Manner in Human Adipocytes
Eicosapentaenoic Acid and Rosiglitazone Increase Adiponectin in an Additive and PPARγ-Dependent Manner in Human Adipocytes
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DOI：
10.1038/oby.2010.186
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发表时间：
2011-02-01
期刊：
影响因子：
6.9
通讯作者：
Robinson, Lindsay E.
中科院分区：
文献类型：
--
作者：
Tishinsky, Justine M.;Ma, David W. L.;Robinson, Lindsay E.
脂联素是一种由脂肪组织分泌的抗炎和胰岛素增敏蛋白，可能受膳食脂肪酸的调节，但其机制尚不完全清楚。我们的目的是研究长链n-3多不饱和脂肪酸（PUFAs）对培养的人脂肪细胞中脂联素的影响，并阐明过氧化物酶体增殖物激活受体-γ（PPAR γ）在这种调节中的作用。将分离的人脂肪细胞与100 μ mol/l二十碳五烯酸（C20：5 n-3，EPA）、二十二碳六烯酸（C22：6 n-3，DHA）、棕榈酸（C16：0）、100 μ mol/l EPA加100 μ mol/l DHA或牛血清白蛋白（对照）一起培养48小时。另外，用单独的或与EPA或DHA结合的PPAR γ拮抗剂（BADGE）或激动剂（罗格列酮）处理脂肪细胞48小时。在48 h时，EPA和DHA分别使脂联素分泌增加了88%和47%（P < 0.05），而EPA（而不是DHA）也使细胞脂联素蛋白增加了136%（P < 0.001）。有趣的是，PPAR γ拮抗作用完全消除了DHA介导的脂联素分泌增加，但仅部分减弱了EPA介导的反应。因此，EPA对脂联素的影响似乎不完全是PPAR γ介导的。罗格列酮增加（P < 0.001）分泌和细胞脂联素蛋白（分别为90%和582%）。最后，EPA和罗格列酮对脂联素分泌的影响是相加的（48 h时合并为+230%，而EPA或罗格列酮单独给药分别为121%和124%）。总的来说，我们的研究结果强调了长链n-3 PUFA单独或与PPAR γ激动剂联合作为脂联素刺激剂的治疗重要性，脂联素是肥胖和相关疾病中的关键脂肪因子。
Adiponectin, an anti-inflammatory and insulin-sensitizing protein secreted from adipose tissue, may be modulated by dietary fatty acids, although the mechanism is not fully known. Our objective was to investigate the effect of long-chain n-3 polyunsaturated fatty acids (PUFAs) on adiponectin in cultured human adipocytes, and to elucidate the role of peroxisome proliferator-activated receptor-gamma(PPAR gamma) in this regulation. Isolated human adipocytes were cultured for 48 h with 100 mu mol/l eicosapentaenoic acid (C20:5n-3, EPA), docosahexaenoic acid (C22:6n-3, DHA), palmitic acid (C16:0), 100 mu mol/l EPA plus 100 mu mol/l DHA, or bovine serum albumin (control). Additionally, adipocytes were treated for 48 h with a PPAR gamma antagonist (BADGE) or agonist (rosiglitazone) in isolation or in conjunction with either EPA or DHA. At 48 h, EPA and DHA increased (P < 0.05) adiponectin secretion by 88 and 47%, respectively, while EPA, but not DHA, also increased (136%, P < 0.001) cellular adiponectin protein. Interestingly, PPAR gamma antagonism completely abolished the DHA-mediated increase in secreted adiponectin, but only partially attenuated the EPA-mediated response. Thus, EPA's effects on adiponectin do not appear to be entirely PPAR gamma mediated. Rosiglitazone increased (P < 0.001) the secreted and cellular adiponectin protein (90 and 582%, respectively). Finally, the effects of EPA and rosiglitazone on adiponectin secretion were additive (+230% at 48 h combined, compared to 121 and 124% by EPA or rosiglitazone alone, respectively). Overall, our findings emphasize the therapeutic importance of long-chain n-3 PUFA alone, or in combination with a PPAR gamma agonist, as a stimulator of adiponectin, a key adipokine involved in obesity and related diseases.