Dietary luteolin activates browning and thermogenesis in mice through an AMPK/PGC1α pathway-mediated mechanism
Dietary luteolin activates browning and thermogenesis in mice through an AMPK/PGC1α pathway-mediated mechanism
复制标题
膳食木犀草素通过 AMPK/PGC1 α 通路介导的机制激活小鼠的褐变和生热作用
DOI：
10.1038/ijo.2016.108
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发表时间：
2016-12-01
影响因子：
4.9
通讯作者：
Liu, J.
中科院分区：
文献类型：
--
作者：
Zhang, X.;Zhang, Q-X;Liu, J.
背景技术背景：两种棕色样脂肪细胞，包括来自棕色脂肪组织的经典棕色脂肪细胞和来自白色脂肪组织的米色细胞，调节产热。棕色样细胞的发育和功能诱导提供了对肥胖和相关代谢疾病的防御。我们先前的研究表明，膳食毛地黄黄酮可以改善饮食诱导的肥胖和胰岛素抵抗小鼠。方法：5周龄雄性C57 BL/6小鼠分别饲喂低脂饲料（LFD）、高脂饲料（HFD）和添加0.01%木犀草素的高脂饲料。12周后，使用联合间接热量测定系统检测他们的能量消耗。此外，产热程序和相关的分子调节剂在脂肪组织进行了评估。在另一项独立研究中，同龄小鼠喂食LFD和含木犀草素的LFD 12周，并研究其能量消耗和产热程序。最后，分化的原代棕色和皮下脂肪细胞被用来确定关键参与的AMPK/PGC 1 α信号在毛地黄黄酮调节的布朗宁和thermogenesics.RESULTS：在喂食HFD或LFD的小鼠，饮食毛地黄黄酮补充增加耗氧量，二氧化碳的产生和呼吸交换率。能量消耗的增强伴随着棕色和皮下脂肪组织中产热基因的上调。同时，几个重要的AMPK/PGC 1 α信号分子被饲料中的毛地黄黄酮激活。此外，毛地黄黄酮治疗直接升高产热基因表达和激活AMPK/PGC 1 α信号在分化的初级棕色和皮下脂肪细胞，而AMPK抑制剂化合物C逆转的efficiency.CONCLUSIONS：饮食毛地黄黄酮激活布朗宁和产热通过AMPK/PGC 1 α途径介导的机制。
BACKGROUND: Two brown-like adipocytes, including classical brown adipocytes from brown adipose tissues and beige cells from white adipose tissues, regulate thermogenesis. The developmental and functional induction of brown-like cells provides a defense against obesity and associated metabolic diseases. Our previous study suggests dietary luteolin can improve diet-induced obesity and insulin resistance in mice. Here we further elucidated the action of the natural flavonoid on energy expenditure and adaptive thermogenesis.METHODS: Five-week-old male C57BL/6 mice were fed low-fat diet (LFD), high-fat diet (HFD) and HFD supplemented with 0.01% luteolin. After 12 weeks, their energy expenditure were detected using a combined indirect calorimetry system. Moreover, thermogenic program and associated molecular regulators were assessed in adipose tissues. In another independent study, even-aged mice were fed LFD and luteolin-containing LFD for 12 weeks, and their energy expenditure and thermogenic program were also investigated. Finally, differentiated primary brown and subcutaneous adipocytes were used to identify the critical participation of AMPK/PGC1 alpha signaling in luteolin-regulated browning and thermogenesis.RESULTS: In mice fed either HFD or LFD, dietary luteolin supplement increased oxygen consumption, carbon dioxide production and respiratory exchange ratio. The enhancement in energy expenditure was accompanied by the upregulation of thermogenic genes in brown and subcutaneous adipose tissues. Meanwhile, several important AMPK/PGC1 alpha signaling molecules were activated by dietary luteolin in the tissues. Further, luteolin treatment directly elevated thermogenic gene expressions and activated AMPK/PGC1 alpha signaling in differentiated primary brown and subcutaneous adipocytes, whereas AMPK inhibitor Compound C reversed the efficiencies.CONCLUSIONS: Dietary luteolin activated browning and thermogenesis through an AMPK/PGC1 alpha pathway-mediated mechanism.