Increased adiponectin secretion by highly purified eicosapentaenoic acid in rodent models of obesity and human obese subjects
Increased adiponectin secretion by highly purified eicosapentaenoic acid in rodent models of obesity and human obese subjects
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DOI：
10.1161/atvbaha.106.136853
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发表时间：
2007-09-01
影响因子：
8.7
通讯作者：
Ogawa, Yoshihiro
中科院分区：
文献类型：
--
作者：
Itoh, Michiko;Suganami, Takayoshi;Ogawa, Yoshihiro
目的-富含n-3多不饱和脂肪酸（PUFAs）或n-3 PUFAs的鱼油已被证明可以降低冠心病的发病率。在这里，我们研究了高度纯化的二十碳五烯酸（EPA）对脂联素，唯一建立的抗动脉粥样硬化和adipocytokine，在啮齿动物模型的肥胖和人类obesity subjects.Methods和结果的生产的影响-我们证明，EPA增加脂联素的分泌在遗传性肥胖ob/ob小鼠和高脂肪饮食诱导的肥胖小鼠。在脂肪细胞和巨噬细胞的体外共培养中，EPA至少部分通过下调巨噬细胞中的肿瘤坏死因子-α来逆转共培养诱导的脂联素分泌减少。我们还发现，在用EPA（每天1.8g）治疗3个月后，人类肥胖受试者的血浆脂联素浓度显著增加。多变量回归分析表明，EPA治疗是唯一的独立决定因素血浆adiponectin concentration.Conclusion -这项研究表明，EPA增加脂联素分泌的啮齿动物模型的肥胖和人类肥胖的主题，可能通过改善肥胖脂肪组织的炎症变化。由于EPA在一项大规模、前瞻性、随机临床试验中降低了主要冠状动脉事件的风险，因此本研究对其在肥胖相关代谢后遗症中的治疗意义提供了重要的见解。
Objectives - Fish oil rich in n-3 polyunsaturated fatty acids (PUFAs) or n-3 PUFAs have been shown to reduce the incidence of coronary heart disease. Here we investigated the effect of highly purified eicosapentaenoic acid (EPA) on production of adiponectin, the only established antiatherogenic and antiinflammatory adipocytokine, in rodent models of obesity and human obese subjects.Methods and Results - We demonstrated that EPA increases adiponectin secretion in genetically obese ob/ob mice and high-fat diet-induced obese mice. In the in vitro coculture of adipocytes and macrophages, EPA reversed the coculture-induced decrease in adiponectin secretion at least in part through downregulation of tumor necrosis factor-alpha in macrophages. We also showed significant increase in plasma adiponectin concentrations in human obese subjects after a 3-month treatment with EPA (1.8 g daily). Multivariate regression analysis revealed that EPA treatment is the only independent determinant of plasma adiponectin concentrations.Conclusion - This study demonstrates that EPA increases adiponectin secretion in rodent models of obesity and human obese subjects, possibly through the improvement of the inflammatory changes in obese adipose tissue. Because EPA has reduced the risk of major coronary events in a large-scale, prospective, randomized clinical trial, this study provides important insight into its therapeutic implication in obesity-related metabolic sequelae.