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槲皮素通过调节丝裂原活化蛋白激酶(MAPK)信号传导对肥胖及肥胖诱导的炎症产生抑制作用。

The inhibitory effects of quercetin on obesity and obesity-induced inflammation by regulation of MAPK signaling.

作者信息

Seo Min-Jung, Lee Yeon-Joo, Hwang Ji-Hyun, Kim Kui-Jin, Lee Boo-Yong

机构信息

Department of Food Science and Biotechnology, CHA University, Seongnam, Kyonggi 463-400, South Korea.

Department of Medicine, Harvard Medical School, Massachusetts General Hospital, Charlestown, MA 02129, USA.

出版信息

J Nutr Biochem. 2015 Nov;26(11):1308-16. doi: 10.1016/j.jnutbio.2015.06.005. Epub 2015 Jul 26.

DOI:10.1016/j.jnutbio.2015.06.005
PMID:26277481
Abstract

Quercetin is a flavonoid found in fruits, vegetables, leaves and grains. It has inhibitory, antiviral, antiasthma, anticancer and antiinflammatory effects. Research has suggested that obesity is linked to metabolic disorders. In this study, we examined the inhibitory effect of quercetin on lipid accumulation and obesity-induced inflammation using 3T3-L1, RAW264.7, zebrafish and mouse models. Quercetin suppressed protein levels of the key adipogenic factors C/EBPβ, C/EBPα, PPARγ and FABP4 and the TG-synthesis enzymes lipin1, DGAT1 and LPAATθ. Activation of m-TOR and p70S6K, which are related to insulin and adipogenesis, was down-regulated during adipogenesis in 3T3-L1 cells. Recent research suggested that MAPK signaling factors were involved in adipogenesis and inflammation and that the adipokines MCP-1 and TNF-α attracted macrophages into adipose tissue. Our data showed that quercetin inhibited the MAPK signaling factors ERK1/2, JNK and p38MAPK and MCP-1 and TNF-α in adipocytes and macrophages. Quercetin also inhibited secretion of the inflammatory cytokines IL-1β and IL-6 and stimulated that of IL-10, an antiinflammatory cytokine. In this study, we confirmed the inhibitory effects of quercetin in adipogenesis and inflammation using a mouse model. In mice, quercetin reduced body weight (almost 40%) and suppressed expression of adipogenic, lipogenic and inflammation-related cytokines. Our data demonstrated that quercetin inhibits lipid accumulation and obesity-induced inflammation in the cell and animal models. Our study suggested that quercetin may represent a potential therapeutic agent for other metabolic disorders by regulating obesity and obesity-induced inflammation.

摘要

槲皮素是一种存在于水果、蔬菜、树叶和谷物中的类黄酮。它具有抑制、抗病毒、抗哮喘、抗癌和抗炎作用。研究表明,肥胖与代谢紊乱有关。在本研究中,我们使用3T3-L1、RAW264.7、斑马鱼和小鼠模型,研究了槲皮素对脂质积累和肥胖诱导炎症的抑制作用。槲皮素抑制关键脂肪生成因子C/EBPβ、C/EBPα、PPARγ和FABP4以及甘油三酯合成酶lipin1、DGAT1和LPAATθ的蛋白水平。在3T3-L1细胞脂肪生成过程中,与胰岛素和脂肪生成相关的m-TOR和p70S6K的激活被下调。最近的研究表明,MAPK信号因子参与脂肪生成和炎症,脂肪因子MCP-1和TNF-α将巨噬细胞吸引到脂肪组织中。我们的数据表明,槲皮素在脂肪细胞和巨噬细胞中抑制MAPK信号因子ERK1/2、JNK和p38MAPK以及MCP-1和TNF-α。槲皮素还抑制炎性细胞因子IL-1β和IL-6的分泌,并刺激抗炎细胞因子IL-10的分泌。在本研究中,我们使用小鼠模型证实了槲皮素在脂肪生成和炎症中的抑制作用。在小鼠中,槲皮素降低了体重(近40%),并抑制了脂肪生成、脂肪生成和炎症相关细胞因子的表达。我们的数据表明,槲皮素在细胞和动物模型中抑制脂质积累和肥胖诱导的炎症。我们的研究表明,槲皮素可能通过调节肥胖和肥胖诱导的炎症,成为治疗其他代谢紊乱的潜在治疗剂。

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