Galloyl Group in B-type Proanthocyanidin Dimers Was Responsible for Its Differential Inhibitory Activity on 3T3-L1 Preadipocytes due to the Strong Lipid Raft-Perturbing Potency

The effects of three B-type proanthocyanidin (PA) dimers covering procyanidin B2 (B-0g), procyanidin B2 3'-O-gallate (B-1g), and procyanidin B2 3,3'-di-O-gallate (B-2g) on 3T3-L1 preadipocyte differentiation and the underlying mechanisms were investigated. The results showed that digalloylated B-type PA dimers (B-2g) strongly inhibited 3T3-L1 preadipocyte differentiation through disrupting the integrity of the lipid raft structure and inhibiting the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα) and then downregulating the expression of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) factors, followed by B-1g, while B-0g had little effect. The different inhibitory effects were mainly due to the difference in the B-type PA dimer structure and the ability to interfere with lipid rafts. The greater the galloylation degree of B-type PA dimers, the stronger the ability to disrupt the lipid raft structure and oppose 3T3-L1 preadipocyte differentiation. In addition, galloylated B-type PA dimers had greater molecular hydrophobicity and topological polarity surface area and could penetrate into the lipid rafts to form multiple hydrogen bonds with the rafts by molecular dynamics simulation. These findings highlighted that the strong lipid raft-perturbing potency of galloylated B-type PA dimers was responsible for inhibition of 3T3-L1 preadipocyte differentiation.