A-type ECG and EGCG dimers inhibit 3T3-L1 differentiation by binding to cholesterol in lipid rafts

文献类型: 外文期刊

第一作者: Zhu, Wei

作者: Zhu, Wei;Deng, Xiangyi;Peng, Jinming;Li, Chunmei;Li, Chunmei;Zou, Bo

作者机构:

关键词: A-type ECG and EGCG dimers;Cholesterol;Disruption;Lipid rafts;3T3-L1 preadipocytes differentiation

期刊名称:JOURNAL OF NUTRITIONAL BIOCHEMISTRY ( 影响因子:6.048; 五年影响因子:6.114 )

ISSN: 0955-2863

年卷期: 2017 年 48 卷

页码:

收录情况: SCI

摘要: The present study aimed to explore the underlying mechanisms of epicatechin-3-gallate-(4 beta -> 8, 2 beta -> O -> 7)-epicatechin-3-gallate (A-type ECG dimer) and epigallocatechin-3-gallate-(4 beta -> 8, 2 beta -> O -> 7)-epigallocatechin-3-gallate (A-type EGCG dimer) involved in their strong inhibitory effects on 3T3-L1 preadipocytes differentiation. In the synthetic "lipid raft-like" liposome, A-type ECG and EGCG dimers incorporated into the liposome with high affinity and decreased the fluidity of the liposome. In 3T3-L1 preadipocytes, A-type ECG and EGCG dimers possibly bonded to lipid rafts cholesterol and disrupted the integrity of lipid rafts, thus exerting their notable inhibitory effects on 3T3-L1 preadipocytes differentiation by suppressing mitotic clonal expansion process and mRNA levels of PPAR gamma, C/EBP alpha, and SREBP1C. A highly positive correlation between the cholesterol binding capacity of the two dimers and their inhibitory effect on 3T3-L1 preadipocytes differentiation (R-2=0.9328) was observed. Molecular dynamics simulation further verified that A-type ECG and EGCG dimers could bond to cholesterol via hydrogen bonding. The results of this study suggested that the disruption of A-type ECG and EGCG dimers on membrane lipid rafts by targeting cholesterol in the lipid rafts was involved in the underlying mechanisms of their strong inhibitory effects on 3T3-L1 preadipocytes differentiation. This broadens the understanding of the molecular mechanisms of polyphenols on modulating and controlling of metabolic dysregulation, particularly adipocyte differentiation, which is a significant risk factor associated with the development of cardiovascular disease. (C) 2017 Elsevier Inc. All rights reserved.

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