Citrus flavonoid naringenin inhibits TLR2 expression in adipocytes
Citrus flavonoid naringenin inhibits TLR2 expression in adipocytes
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DOI：
10.1016/j.jnutbio.2012.10.003
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发表时间：
2013-07-01
影响因子：
5.6
通讯作者：
Kurokawa, Masahiko
中科院分区：
文献类型：
--
作者：
Yoshida, Hiroki;Watanabe, Wataru;Kurokawa, Masahiko
最近发现，Toll样受体(Toll-like Receptor，TLRs)参与了肥胖引起的脂肪组织炎症，从而导致胰岛素抵抗和2型糖尿病的发生。因此，适当调节TLR的表达或激活是改善肥胖相关疾病的重要策略。在这篇报道中，我们发现柑橘类黄酮类成分--柚皮苷在脂肪细胞分化过程中抑制TLR2的表达。这种作用部分是通过激活过氧化物体增殖物激活的受体伽马来实现的。此外，柚皮苷元还可抑制分化脂肪细胞与巨噬细胞共培养诱导的TLR2表达，也可通过抑制分化脂肪细胞核因子-kappaB和c-jun NH2末端激酶通路的激活来抑制肿瘤坏死因子-α(TNF-α)诱导的TLR2表达。此外，柚皮苷元还能降低高脂饮食小鼠脂肪组织中TLR2的表达。这些结果与改善高血糖和抑制炎症介质，包括肿瘤坏死因子-α和单核细胞趋化蛋白-1有关。综上所述，这些数据表明，柚皮苷元具有抗炎作用，可能是通过抑制脂肪细胞中TLR2的表达。我们的发现表明，柚皮苷元对肥胖相关疾病起到有益作用的分子机制。(C)2013 Elsevier Inc.保留所有权利。
Toll-like receptors (TLRs) were recently shown to be involved in obesity-induced inflammation in adipose tissue, which contributes to the development of insulin resistance and type 2 diabetes. Thus, the appropriate regulation of TLR expression or activation is an important strategy for improving obesity-related diseases. In this report, we show that naringenin, a citrus flavonoid, inhibits TLR2 expression during adipocyte differentiation. This effect is mediated in part through peroxisome proliferator-activated receptor gamma activation. In addition, naringenin suppresses TLR2 expression induced by the co-culture of differentiated adipocytes and macrophages and also inhibits tumor necrosis factor-alpha (TNF-alpha)-induced TLR2 expression by inhibiting the activation of nuclear factor-kappa B and c-Jun NH2-terminal kinase pathways in differentiated adipocytes. Furthermore, naringenin decreases TLR2 expression in adipose tissue of high-fat diet-fed mice. These results are correlated with the improvement of hyperglycemia and the suppression of inflammatory mediators, including TNF-alpha and monocyte chemotactic protein-1. Taken together, these data suggest that naringenin exhibits anti-inflammatory properties, presumably by inhibiting TLR2 expression in adipocytes. Our findings suggest a molecular mechanism by which naringenin exerts beneficial effects against obesity-related diseases. (C) 2013 Elsevier Inc. All rights reserved.