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.