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 aims 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 are fed a high‐fat diet (HFD) and GC‐(4→8)‐GCG (40 or 80 mg kg⁻¹ d⁻¹) for 8 weeks. The metabolic profiles, adipose tissue hypertrophy, macrophage infiltration, and inflammatory cytokine production are investigated. Additionally, 3T3‐L1 preadipocytes are 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 decreases HFD‐induced epididymal white adipose tissue (eWAT) hypertrophy, suppresses proinflammatory cytokine production and macrophage infiltration in eWAT, and improves insulin sensitivity in HFD‐induced obese mice. In vitro, GC‐(4→8)‐GCG shows 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 can modulate obesity and improve obesity‐related insulin resistance by inhibiting preadipocyte differentiation and the related proinflammatory responses.