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 β-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.

中文翻译：

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木犀草素通过促进中央5-羟色胺途径减少秀丽隐杆线虫的脂肪储存。

5-羟色胺在调节能量稳态和脂肪代谢中起关键作用。各种饮食中的类黄酮，例如木犀草素和槲皮素，具有潜在的抗肥胖特性。然而，尚不清楚类黄酮是否通过中央5-羟色胺信号传导发挥其抗肥胖作用。在这里，我们采用经典的线虫秀丽隐杆线虫模型，评估了六种饮食类黄酮（黄酮芹菜素，黄体素，木犀草素和黄酮醇山emp酚，杨梅素和槲皮素）对脂肪蓄积的影响。剂量依赖性研究表明，在所测试的类黄酮中，六种类黄酮对秀丽隐杆线虫脂肪积累具有实质性抑制作用，而木犀草素的抑制作用最强。同时，类黄酮处理对蠕虫的生长，繁殖力和摄食没有明显的影响。此外，tph-1的突变，它编码5-羟色胺合成的保守限速酶，完全消除了木犀草素诱导的脂肪减少，但不影响其他五个类黄酮的脂肪减少。在野生型N2蠕虫中，木犀草素处理不仅提高了tph-1的表达，而且还提高了与血清素相关的两个受体mod-1和ser-6的mRNA水平，它们在血清素介导的脂肪中起特定作用减少。mod-1或ser-6的突变也完全消除了木犀草素引起的脂肪减少。最后，我们发现木犀草素处理可提高ADF神经元中5-羟色胺的合成，从而促进秀丽隐杆线虫的脂解作用和脂肪酸β-氧化。总之，结果表明木犀草素通过促进中央5-羟色胺信号传导减少线虫的脂肪存储，