Regulation of mitotic clonal expansion and thermogenic pathway are involved in the antiadipogenic effects of cyanidin-3-O-glucoside

Abstract

Introduction: Obesity is a metabolic disease with an increase both in cell size (hypertrophy) and in cell number (hyperplasia) following differentiation of new adipocytes. Adipogenesis is a well-orchestrated program in which mitotic clonal expansion (MCE) occurs in the early step followed by the late terminal differentiation one. Methods: Aim of the study was to evaluate the in vitro effects of cyanidin-3-O-glucoside (C3G), an anthocyanin present in many fruits and vegetables, in the early or late phase of 3T3-L1 preadipocytes differentiation. Results: C3G exposure in the early phase of adipogenesis process induced a more marked reduction of CCAAT/enhancer-binding protein-β (C/EBPβ), peroxisome proliferator-activated receptor γ (PPAR-ɣ) and fatty acid synthase (Fasn) expression than late phase exposure and these effects were associated to a reduced MCE with cell cycle arrest at G0/G1 phase via p21 expression. Furthermore, C3G exposure during the early phase activated AMP-activated protein kinase (AMPK) pathway better than in the late phase promoting the enhancement of beige-like adipocytes. In fact, C3G induced thermogenic biomarkers uncoupling protein-1 (Ucp1) and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (Pgc1) and these effects were more evident during early phase exposure. Conclusion: Our data demonstrate that C3G reduces the terminal adipogenic process affecting the early phase of differentiation and inducing a thermogenic program.