从海带中分离出的岩藻甾醇通过调节3T3-L1脂肪细胞中的FoxO1信号通路抑制脂肪生成。

Fucosterol, isolated from Ecklonia stolonifera, inhibits adipogenesis through modulation of FoxO1 pathway in 3T3-L1 adipocytes.

作者信息

Lee Ji-Hyun, Jung Hyun Ah, Kang Min Jae, Choi Jae Sue, Kim Gun-Do

机构信息

Department of Microbiology, College of Natural Sciences, Pukyong National University, Busan, Korea.

Department of Food Science and Human Nutrition, College of Environmental and Bioresource Sciences, Chonbuk National University, Jeonju, Korea.

出版信息

J Pharm Pharmacol. 2017 Mar;69(3):325-333. doi: 10.1111/jphp.12684. Epub 2017 Jan 30.

DOI:10.1111/jphp.12684

PMID:28134973

Abstract

OBJECTIVES

The purpose of this study was to investigate the effects of fucosterol on adipogenesis of 3T3-L1 preadipocytes and its underlying mechanisms.

METHODS

Fucosterol, isolated from brown algae, Ecklonia stolonifera. We investigated the levels of lipid accumulation using Oil Red O staining. We conducted Western blot analysis to investigate regulatory effects of fucosterol on expression of phosphoinositide 3-kinase (PI3K), Akt, extracellular signal-regulated kinase (ERK), forkhead box protein O 1 (FoxO1) in 3T3-L1 adipocytes.

KEY FINDINGS

Fucosterol significantly reduced intracellular lipid accumulation of 3T3-L1 adipocytes at concentrations of 25 and 50 μm. Fucosterol downregulated insulin-triggered PI3K/Akt, and ERK pathways. It subsequently decreased expression of adipogenic transcription factors, including PPARγ, C/EBPα and SREBP-1. In addition, fucosterol enhanced SirT1 expression while decreased phospho-FoxO1 expression which resulted in the activation of FoxO1.

CONCLUSIONS

We revealed that fucosterol inhibited adipogenesis of 3T3-L1 preadipocytes through modulation of FoxO signalling pathway. Therefore, our results suggest that fucosterol may be used for novel agents for the treatment of obesity.

摘要

目的

本研究旨在探讨岩藻甾醇对3T3-L1前脂肪细胞脂肪生成的影响及其潜在机制。

方法

从褐藻海带中分离出岩藻甾醇。我们使用油红O染色来研究脂质积累水平。我们进行蛋白质免疫印迹分析，以研究岩藻甾醇对3T3-L1脂肪细胞中磷酸肌醇3激酶（PI3K）、蛋白激酶B（Akt）、细胞外信号调节激酶（ERK）、叉头框蛋白O1（FoxO1）表达的调节作用。

主要发现

在25和50μm浓度下，岩藻甾醇显著降低了3T3-L1脂肪细胞的细胞内脂质积累。岩藻甾醇下调胰岛素触发的PI3K/Akt和ERK信号通路。随后，它降低了包括过氧化物酶体增殖物激活受体γ（PPARγ）、CCAAT/增强子结合蛋白α（C/EBPα）和固醇调节元件结合蛋白-1（SREBP-1）在内的脂肪生成转录因子的表达。此外，岩藻甾醇增强了沉默调节蛋白1（SirT1）的表达，同时降低了磷酸化FoxO1的表达，从而导致FoxO1的激活。