School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China; Academy of Chinese Medical Science, Zhejiang Chinese Medical University, China.
Academy of Chinese Medical Science, Zhejiang Chinese Medical University, China.
Biochim Biophys Acta Mol Cell Biol Lipids. 2023 Sep;1868(9):159364. doi: 10.1016/j.bbalip.2023.159364. Epub 2023 Jul 9.
Adipocyte browning increases energy expenditure by thermogenesis, which has been considered a potential strategy against obesity and its related metabolic diseases. Phytochemicals derived from natural products with the ability to improve adipocyte thermogenesis have aroused extensive attention. Acteoside (Act), a phenylethanoid glycoside, exists in various medicinal or edible plants and has been shown to regulate metabolic disorders. Here, the browning effect of Act was evaluated by stimulating beige cell differentiation from the stromal vascular fraction (SVF) in the inguinal white adipose tissue (iWAT) and 3T3-L1 preadipocytes, and by converting the iWAT-SVF derived mature white adipocytes. Act improves adipocyte browning by differentiation of the stem/progenitors into beige cells and by direct conversion of mature white adipocytes into beige cells. Mechanistically, Act inhibited CDK6 and mTOR, and consequently relieved phosphorylation of the transcription factor EB (TFEB) and increased its nuclear retention, leading to induction of PGC-1α, a driver of mitochondrial biogenesis, and UCP1-dependent browning. These data thus unveil a CDK6-mTORC1-TFEB pathway that regulates Act-induced adipocyte browning.
脂肪细胞棕色化通过产热增加能量消耗，这被认为是对抗肥胖及其相关代谢性疾病的一种潜在策略。具有改善脂肪细胞产热能力的天然产物衍生的植物化学物质引起了广泛关注。毛蕊花糖苷（Act）是苯乙醇苷类化合物，存在于各种药用或食用植物中，已被证明可调节代谢紊乱。在这里，通过刺激腹股沟白色脂肪组织（iWAT）和 3T3-L1 前体脂肪细胞的基质血管部分（SVF）中的米色细胞分化，以及将 iWAT-SVF 衍生的成熟白色脂肪细胞转化，评估了 Act 的棕色化作用。Act 通过将干细胞/祖细胞分化为米色细胞，以及直接将成熟的白色脂肪细胞转化为米色细胞，来改善脂肪细胞的棕色化。在机制上，Act 抑制 CDK6 和 mTOR，从而减轻转录因子 EB（TFEB）的磷酸化并增加其核保留，导致线粒体生物发生的驱动因子 PGC-1α和 UCP1 依赖性棕色化的诱导。这些数据揭示了一个调节 Act 诱导的脂肪细胞棕色化的 CDK6-mTORC1-TFEB 通路。
