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植物固醇通过激活高脂肪饮食喂养的小鼠的 AMP 激活蛋白激酶(AMPK)α 来刺激白色脂肪细胞的褐色化。

Phytol stimulates the browning of white adipocytes through the activation of AMP-activated protein kinase (AMPK) α in mice fed high-fat diet.

机构信息

Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, P. R. China and ALLTECH-SCAU Animal Nutrition Control Research Alliance and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou 510642, P. R. China.

出版信息

Food Funct. 2018 Apr 25;9(4):2043-2050. doi: 10.1039/C7FO01817G.

DOI:10.1039/C7FO01817G
PMID:29570193
Abstract

Stimulating the browning of white adipocytes contributes to the restriction of obesity and related metabolic disorders. This study aimed to investigate the browning effects of phytol on mice inguinal subcutaneous white adipose tissue (iWAT) and explore the underlying mechanisms. Our results demonstrated that phytol administration decreased body weight gain and iWAT index, and stimulated the browning of mice iWAT, with the increased expression of brown adipocyte marker genes (UCP1, PRDM16, PGC1α, PDH, and Cyto C). In addition, phytol treatment activated the AMPKα signaling pathway in mice iWAT. In good agreement with the in vivo findings, the in vitro results showed that 100 μM phytol stimulated brown adipogenic differentiation and formation of brown-like adipocytes in the differentiated 3T3-L1 by increasing the mitochondria content and oxygen consumption, and promoting mRNA and/or protein expression of brown adipocyte markers (UCP1, PRDM16, PGC1α, PDH, Cyto C, Cidea and Elovl3) and beige adipocyte markers (CD137 and TMEM26). Meanwhile, phytol activated the AMPKα signaling pathway in the differentiated 3T3-L1. However, the inhibition of AMPKα with Compound C totally abolished phytol-stimulated brown adipogenic differentiation and formation of brown-like adipocytes. In conclusion, these results showed that phytol stimulated the browning of mice iWAT, which was coincident with the increased formation of brown-like adipocytes in the differentiated 3T3-L1, and appeared to be primarily mediated by the AMPKα signaling pathway. These data provided new insight into the role of phytol in regulating the browning of WAT and suggested the potential application of phytol as a nutritional intervention for the restriction of obesity and related metabolic disorders.

摘要

刺激白色脂肪棕色化有助于限制肥胖及其相关代谢紊乱。本研究旨在探究叶绿醇对小鼠腹股沟皮下白色脂肪组织(iWAT)的棕色化作用,并探讨其潜在机制。研究结果表明,叶绿醇给药可降低体重增加和 iWAT 指数,并刺激小鼠 iWAT 的棕色化,棕色脂肪细胞标记基因(UCP1、PRDM16、PGC1α、PDH 和 Cyto C)的表达增加。此外,叶绿醇处理激活了小鼠 iWAT 中的 AMPKα 信号通路。与体内研究结果一致,体外结果表明,100μM 叶绿醇通过增加线粒体含量和耗氧量,促进棕色脂肪细胞标记基因(UCP1、PRDM16、PGC1α、PDH、Cyto C、Cidea 和 Elovl3)和米色脂肪细胞标记基因(CD137 和 TMEM26)的 mRNA 和/或蛋白表达,刺激分化的 3T3-L1 中的棕色脂肪生成和棕色样脂肪细胞形成。同时,叶绿醇激活了分化的 3T3-L1 中的 AMPKα 信号通路。然而,用化合物 C 抑制 AMPKα 完全消除了叶绿醇刺激的棕色脂肪生成和棕色样脂肪细胞形成。综上所述,这些结果表明,叶绿醇刺激了小鼠 iWAT 的棕色化,与分化的 3T3-L1 中棕色样脂肪细胞的形成增加相一致,这似乎主要是通过 AMPKα 信号通路介导的。这些数据为叶绿醇在调节 WAT 棕色化中的作用提供了新的见解,并表明叶绿醇作为一种营养干预措施,具有限制肥胖及其相关代谢紊乱的潜在应用。

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