title: A-type ECG and EGCG dimers disturb the structure of 3T3-L1 cell membrane and strongly inhibit its differentiation by targeting peroxisome proliferator-activated receptor γ with miR-27 involved mechanism.
abstract: The effects of four proanthocyanidin dimers including epicatechin-(4β→8, 2β→O→7)-epicatechin (A-type EC dimer), epicatechin-(4β→8)-epicatechin (B-type EC dimer), epicatechin-3-gallate-(4β→8, 2β→O→7)-epicatechin-3-gallate (A-type ECG dimer) and epigallocatechin-3-gallate-(4β→8, 2β→O→7)-epigallocatechin-3-gallate (A-type EGCG dimer) on 3T3-L1 preadipocyte cell differentiation and the underlying mechanisms were explored and compared. The results showed that A-type ECG dimer and A-type EGCG dimer significantly reduced the intracellular lipid accumulation in 3T3-L1 preadipocyte cells by targeting miR-27a and miR-27b as well as peroxisome proliferator-activated receptor γ (PPARγ) in the early stage of differentiation, while A-type EC dimer and B-type EC dimer showed little effect. In addition, our results revealed that the inhibitory effects of proanthocyanidin dimers on 3T3-L1 preadipocyte differentiation were highly structure-dependent and the effects were associated with the dimer-membrane interactions. The presence of galloyl moieties and A-type linkage within the structure of proanthocyanidins might be crucial for their inhibitory effect on adipogenesis. The strong disturbing effects of A-type ECG and A type EGCG dimers on the fluidity, hydrophobicity and permeability of membrane of 3T3-L1 preadipocyte cell were at least, in part, responsible for their distinct inhibitory effects on adipocyte hyperplasia.
authors.affiliation: College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.affiliation: College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China; Key Laboratory of Functional Foods, Ministry of Agriculture, Guangdong Key Laboratory of Agricultural Products Processing, Sericultural & Agri-Food Research Institute Guangdong Academy of Agricultural Sciences, Guangzhou 510610, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zou
authors.affiliation: College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Rongzu
authors.initials: R
authors.lastname: Nie
authors.affiliation: College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China; Key Laboratory of Environment Correlative Food Science (Huazhong Agricultural University), Ministry of Education, Wuhan, China. Electronic address: lichmyl@mail.hzau.edu.cn.
authors.forename: Chun-mei
authors.initials: CM
authors.lastname: Li
mesh_terms: D041721:3T3-L1 Cells / Q000187:drug effects; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D019281:Dimerization; D051379:Mice; D035683:MicroRNAs / Q000235:genetics; D047495:PPAR gamma / Q000378:metabolism
chemical_list: D035683:MicroRNAs; C540674:Mirn27 microRNA, mouse; D047495:PPAR gamma; D002392:Catechin; C062669:epicatechin gallate; C045651:epigallocatechin gallate
keywords: Adipogenesis; Membrane disturbing effects; MicroRNAs; PPARγ; Structural-dependent