非酒精性脂肪肝（NAFLD）已与肝脏脂肪积累和脂质代谢失衡相关。芝麻素是一种常见于芝麻油中的木脂素，具有抗氧化、抗炎和抗癌特性。然而，芝麻素预防肝脏脂肪肝的精确机制尚不明确。本研究旨在探索芝麻素改善脂质代谢失调的分子机制。通过将HepG2细胞暴露于棕榈酸钠，建立了体外肝脂肪肝模型。结果显示，芝麻素有效减轻了脂质毒性并降低了活性氧的产生。此外，芝麻素通过调节脂肪酸合成酶（FASN）、甾体类调节元件结合蛋白1c（SREBP-1c）、Forkhead盒蛋白O-1和脂肪脂肪酸酯水解酶等关键因子来抑制脂质积累。分子对接结果表明，芝麻素可以与雌激素受体α（ERα）结合，并通过钙/钙调素依赖蛋白激酶激酶β（CaMKKβ）/AMP激活蛋白激酶（AMPK）信号通路来降低FASN和SREBP-1c的表达。芝麻素通过激活ERα/CaMKKβ/AMPK信号通路，在HepG2细胞中减轻了棕榈酸诱导的脂质毒性并调节了肝脏脂质代谢。这些发现提示芝麻素可以改善脂质代谢紊乱，并成为治疗肝脏脂肪肝的有前景的候选药物。© 2023 Elsevier公司保留所有权利。

Nonalcoholic fatty liver disease (NAFLD) has been linked to fat accumulation in the liver and lipid metabolism imbalance. Sesamin, a lignan commonly found in sesame seed oil, possesses antioxidant, anti-inflammatory, and anticancer properties. However, the precise mechanisms by which sesamin prevents hepatic steatosis are not well understood. This study aimed to explore the molecular mechanisms by which sesamin may improve lipid metabolism dysregulation. A in vitro hepatic steatosis model was established by exposing HepG2 cells to palmitate sodium. The results showed that sesamin effectively mitigated lipotoxicity and reduced reactive oxygen species production. Additionally, sesamin suppressed lipid accumulation by regulating key factors involved in lipogenesis and lipolysis, such as fatty acid synthase (FASN), sterol regulatory element-binding protein 1c (SREBP-1c), forkhead box protein O-1, and adipose triglyceride lipase. Molecular docking results indicated that sesamin could bind to estrogen receptor α (ERα) and reduce FASN and SREBP-1c expression via the Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ)/ AMP-activated protein kinase (AMPK) signaling pathway. Sesamin attenuated palmitate-induced lipotoxicity and regulated hepatic lipid metabolism in HepG2 cells by activating the ERα/CaMKKβ/AMPK signaling pathway. These findings suggest that sesamin can improve lipid metabolism disorders and is a promising candidate for treating hepatic steatosis.Copyright © 2023 Elsevier Inc. All rights reserved.