Luteolin reduces fat storage in Caenorhabditis elegans by promoting the central serotonin pathway
Luteolin reduces fat storage in Caenorhabditis elegans by promoting the central serotonin pathway
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木犀草素通过促进中枢血清素途径减少秀丽隐杆线虫的脂肪储存
DOI：
10.1039/c9fo02095k
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发表时间：
2020-01-01
期刊：
影响因子：
6.1
通讯作者：
Liu, Jian
中科院分区：
文献类型：
--
作者：
Lin, Yan;Yang, Nan;Liu, Jian
血清素在调节能量平衡和脂肪代谢中起着关键作用。各种膳食类黄酮，例如木犀草素和槲皮素，具有潜在的抗肥胖特性。然而，目前还不清楚类黄酮是否通过中枢5-羟色胺信号传导发挥其抗肥胖作用。采用经典的动物模型C.为了评估六种膳食类黄酮（黄酮类芹菜素、白杨素和木犀草素以及黄酮醇类山奈酚、杨梅素和槲皮素）对脂肪积累的影响，我们在线虫中进行了实验。剂量依赖性研究表明，6种黄酮类化合物对C.在供试的黄酮类化合物中，毛地黄黄酮的抑制活性最强。黄酮类化合物处理对蚯蚓的生长、繁殖和摄食无明显影响。此外，编码5-羟色胺合成的保守限速酶tph-1的突变完全消除了木犀草素诱导的脂肪减少，但不影响其他五种黄酮类化合物的脂肪减少。在野生型N2蠕虫中，毛地黄黄酮处理不仅提高了tph-1的表达，而且还提高了mod-1和ser-6的mRNA水平，这两种受体是阿托宁相关的受体，在阿托宁介导的减脂中发挥特定作用。mod-1或ser-6的突变也完全消除了木犀草素诱导的脂肪减少。最后，我们发现毛地黄黄酮处理增加ADF神经元中5-羟色胺的合成，从而促进C.优雅的总之，结果表明，毛地黄黄酮减少C。elegans脂肪储存通过促进中央5-羟色胺信号，这表明新的见解阐明机制的基础脂肪调节毛地黄黄酮。
Serotonin plays a critical role in regulating energy homeostasis and fat metabolism. Various dietary flavonoids, e.g. luteolin and quercetin, possess potential anti-obesity properties. However, it is unclear whether the flavonoids exert their anti-obesity actions via central serotonin signaling. Here, employing a classic animal model C. elegans, we assessed the effects of six dietary flavonoids (flavones apigenin, chrysin, and luteolin and flavonols kaempferol, myricetin, and quercetin) on fat accumulation. The dose-dependent study revealed the substantial inhibitory actions of the six flavonoids on C. elegans fat accumulation and the strongest inhibitory activity of luteolin among the tested flavonoids. Meanwhile, flavonoid treatments did not have an obvious influence on worm growth, fecundity and feeding. Furthermore, the mutation of tph-1, which encodes the conserved rate-limiting enzyme of serotonin synthesis, fully abolished luteolin-induced fat loss but did not affect fat reduction by the other five flavonoids. In wild-type N2 worms, luteolin treatment not only elevated the expression of tph-1, but also enhanced the mRNA levels of mod-1 and ser-6, which are two serotonin-related receptors and play specific roles in serotonin-mediated fat reduction. The mutation of either mod-1 or ser-6 also fully abolished luteolin-induced fat loss. Finally, we found that luteolin treatment elevated serotonin synthesis in ADF neurons to promote lipolysis and fatty acid beta-oxidation in C. elegans. Together, the results indicated that luteolin reduced C. elegans fat storage by promoting central serotonin signaling, suggesting new insights into elucidating the mechanism underlying fat regulation by luteolin.