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钝叶桂活性提取物通过持续的 Wnt 信号通路抑制脂肪生成,并在 3T3-L1 前脂肪细胞中发挥抗炎作用。

An active extract of Lindera obtusiloba inhibits adipogenesis via sustained Wnt signaling and exerts anti-inflammatory effects in the 3T3-L1 preadipocytes.

机构信息

Department of Gastroenterology, Infectiology and Rheumatology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, 12200 Berlin, Germany.

出版信息

J Nutr Biochem. 2010 Dec;21(12):1170-7. doi: 10.1016/j.jnutbio.2009.09.013. Epub 2010 Jan 25.

Abstract

Obesity, the related metabolic syndrome and associated liver diseases represent an epidemic problem and demand for effective therapeutic strategies. In this regard, natural compounds derived from Oriental medicine such as green tea polyphenols influencing adipogenesis attract growing attention. In Korea, an aqueous extract from the Japanese spice bush Lindera obtusiloba is traditionally used for treatment of inflammation and prevention of liver damage. We here investigated effects of the L. obtusiloba extract on cell growth, apoptosis, Wnt signaling and differentiation of (im)mature adipocytes using 3T3-L1, an established cell line for studying adipogenesis. L. obtusiloba extract reduced the de novo DNA synthesis of 3T3-L1 preadipocytes in a concentration dependent manner with an IC(50) of ∼135 μg/ml paralleled by induction of caspase 3/7 mediated apoptosis. Hormone-induced 3T3 L1 differentiation in the presence of L. obtusiloba extract resulted in a reduced accumulation of intracellular lipid droplets by 70%, in down-regulated expression of the adipogenesis-associated proteins glucose transporter-4 and vascular endothelial growth factor, in reduced secretion of the proadipogenic matrix metalloproteinase-2, and in dampened phosphorylation of the Wnt pathway effector protein β-catenin with subsequent diminished expression of the peroxisome proliferator-activated receptor-γ. Treatment of mature adipocytes with L. obtusiloba extract also significantly reduced intracellular lipid droplets. In addition to this strong interference of L. obtusiloba extract with adipogenesis, L. obtusiloba extract exerted anti-inflammatory effects. L. obtusiloba extract significantly attenuated lipopolysaccharide- and tumor necrosis factor α-induced secretion of IL-6 by preadipocytes, thus influencing insulin resistance and inflammatory state characterizing obesity. In conclusion, extracts of L. obtusiloba should be evaluated as a potential complementary treatment option for obesity associated with the metabolic syndrome.

摘要

肥胖症、相关代谢综合征和相关肝病是一个流行问题,需要有效的治疗策略。在这方面,源自东方医学的天然化合物,如影响脂肪生成的绿茶多酚,引起了越来越多的关注。在韩国,传统上使用日本杨桐 Lindera obtusiloba 的水提取物来治疗炎症和预防肝损伤。我们在这里研究了 L. obtusiloba 提取物对 3T3-L1 细胞生长、凋亡、Wnt 信号和(未)成熟脂肪细胞分化的影响,3T3-L1 是研究脂肪生成的成熟细胞系。L. obtusiloba 提取物以浓度依赖的方式减少 3T3-L1 前脂肪细胞的新 DNA 合成,IC50 约为 135μg/ml,同时诱导 caspase 3/7 介导的凋亡。在 L. obtusiloba 提取物存在的情况下,激素诱导的 3T3 L1 分化导致细胞内脂滴的积累减少 70%,脂肪生成相关蛋白葡萄糖转运蛋白-4 和血管内皮生长因子的表达下调,促脂肪生成的基质金属蛋白酶-2 的分泌减少,Wnt 通路效应蛋白β-catenin 的磷酸化减弱,随后过氧化物酶体增殖物激活受体-γ的表达减少。用 L. obtusiloba 提取物处理成熟脂肪细胞也显著减少细胞内脂滴。除了强烈干扰脂肪生成外,L. obtusiloba 提取物还具有抗炎作用。L. obtusiloba 提取物显著减弱了前脂肪细胞中脂多糖和肿瘤坏死因子-α诱导的 IL-6 的分泌,从而影响肥胖症中特征性的胰岛素抵抗和炎症状态。总之,L. obtusiloba 提取物应作为治疗肥胖症相关代谢综合征的潜在补充治疗选择进行评估。

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