GC-(4→8)-GCG, A Proanthocyanidin Dimer from Camellia ptilophylla, Modulates Obesity and Adipose Tissue Inflammation in High-fat Diet Induced Obese Mice.

SCOPE: Excessive fat accumulation in adipose tissue leads to obesity and related chronic inflammation. This study aimed to examine the effects of gallocatechin -(4→8)-gallocatechin-3-O-gallate (GC-(4→8)-GCG), a main proanthocyanidin dimer from Camellia ptilophylla (Cocoa tea), on adipocyte- and adipose-related inflammation in vivo and in vitro.

METHODS AND RESULTS: C57BL/6 mice were fed a high-fat diet (HFD) and GC-(4→8)-GCG (40 or 80 mg/kg/d) for 8 weeks. The metabolic profiles, adipose tissue hypertrophy, macrophage infiltration, and inflammatory cytokine production were investigated. Additionally, 3T3-L1 preadipocytes were utilized to investigate the effect of GC-(4→8)-GCG on preadipocyte differentiation and the tumor necrosis factor (TNF)-α-stimulated inflammatory response in vitro. GC-(4→8)-GCG supplementation decreased HFD-induced epididymal white adipose tissue (eWAT) hypertrophy, suppressed proinflammatory cytokine production and macrophage infiltration in eWAT, and improved insulin sensitivity in HFD-induced obese mice. In vitro, GC-(4→8)-GCG showed a strong anti-adipogenic potential in 3T3-L1 preadipocyte by inhibiting the expression of key adipogenic transcription factors and decreasing the production of proinflammatory cytokines by inhibiting the activation of the nuclear factor (NF)-κB, Janus tyrosine kinase/signal transducer and activator of transcription (JAK/STAT3) and mitogen-activated protein kinase (MAPK) signaling pathways.

CONCLUSION: GC-(4→8)-GCG could modulate obesity and improve obesity-related insulin resistance by inhibiting preadipocyte differentiation and the related proinflammatory responses. This article is protected by copyright. All rights reserved.