Metabolic-associated fatty liver disease (MAFLD) is witnessing a global surge; however, it still lacks effective pharmacological interventions. Fucoxanthin, a natural bioactive metabolite derived from marine brown algae, exhibits promising pharmacological functions, particularly in ameliorating metabolic disorders. However, the mechanisms underlying its therapeutic efficacy in addressing MAFLD remain elusive. Our present findings indicated that fucoxanthin significantly alleviated palmitic acid (PA)-induced hepatic lipid deposition in vitro and obesity-induced hepatic steatosis in ob/ob mice. Moreover, at both the protein and transcriptional levels, fucoxanthin effectively increased the expression of PPARα and CPT1 (involved in fatty acid oxidation) and suppressed FASN and SREBP1c (associated with lipogenesis) in both PA-induced HepG2 cells and hepatic tissues in ob/ob mice. This modulation was accompanied by the activation of AMPK. The capacity of fucoxanthin to improve hepatic lipid deposition was significantly attenuated when utilizing the AMPK inhibitor or siRNA-mediated AMPK silencing. Mechanistically, fucoxanthin activates AMPK, subsequently regulating the KEAP1/Nrf2/ARE signaling pathway to exert antioxidative effects and stimulating the PGC1α/NRF1 axis to enhance mitochondrial biogenesis. These collective actions contribute to fucoxanthin’s amelioration of hepatic steatosis induced by metabolic perturbations. These findings offer valuable insights into the prospective utilization of fucoxanthin as a therapeutic strategy for managing MAFLD.

中文翻译：

---

岩藻黄质减轻代谢相关脂肪肝疾病脂质沉积的分子机制


代谢相关脂肪肝病（MAFLD）正在全球范围内激增；然而，仍然缺乏有效的药物干预措施。岩藻黄质是一种源自海洋褐藻的天然生物活性代谢物，具有良好的药理功能，特别是在改善代谢紊乱方面。然而，其治疗 MAFLD 的功效背后的机制仍然难以捉摸。我们目前的研究结果表明，岩藻黄质可显着减轻棕榈酸 (PA) 诱导的体外肝脏脂质沉积和肥胖诱导的ob/ob小鼠肝脏脂肪变性。此外，在蛋白质和转录水平上，岩藻黄质有效增加 PA 诱导的 HepG2 细胞和ob/ob肝组织中 PPARα 和 CPT1（参与脂肪酸氧化）的表达，并抑制 FASN 和 SREBP1c（与脂肪生成相关）。老鼠。这种调节伴随着 AMPK 的激活。当使用 AMPK 抑制剂或 siRNA 介导的 AMPK 沉默时，岩藻黄质改善肝脏脂质沉积的能力显着减弱。从机制上讲，岩藻黄质激活 AMPK，随后调节 KEAP1/Nrf2/ARE 信号通路发挥抗氧化作用，并刺激 PGC1α/NRF1 轴增强线粒体生物发生。这些集体作用有助于岩藻黄质改善代谢紊乱引起的肝脏脂肪变性。这些发现为岩藻黄质作为 MAFLD 治疗策略的前瞻性应用提供了宝贵的见解。