Cocoa Shell Phenolic Compounds Preserve Mitochondrial Function and Insulin Sensitivity in Adipocytes by Attenuating Their Inflammatory Interplay with Macrophages (FS15-06-19)

Abstract

ObjectivesThe objective was to evaluate the effect of an aqueous phenolic extract from cocoa shell (CAE) and its main phenolic compounds to prevent the adipogenesis-induced loss of mitochondrial function and insulin sensitivity, targeting the inflammatory interplay macrophages-adipocytes in vitro. MethodsCAE and its main phenolic compounds (protocatechuic acid, procyanidin B2, and epicatechin) were tested in cell culture of RAW264.7 macrophages and 3T3-L1 mature adipocytes. Macrophages were stimulated with lipopolysaccharide (LPS, 1 μg/mL). Adipocytes were treated with the conditioned media (CM) from LPS-stimulated macrophages. Biomarkers for inflammation, mitochondrial function, and insulin sensitivity were determined after 24 h co-treatment with CAE and LPS/CM using chemical and immunochemical techniques. ResultsLPS-stimulated macrophages showed reduced inducible nitric oxide synthase and cyclooxygenase-2 expression and lowered NO and pro-inflammatory cytokines release when treated with CAE and pure phenolics. Inflammatory crosstalk created by stimulating adipocytes with CM was arrested; CAE diminished tumor necrosis factor-α (67%, p < 0.05) and highly promoted adiponectin secretion (12.3-fold, p < 0.05). Mitochondrial function, measured by reactive oxygen species production, mitochondrial content, and activity, was preserved in CM-treated adipocytes through up-regulating peroxisome proliferator-activated receptor gamma coactivator 1-α expression (46%, p < 0.05). Significant (p < 0.05) increases in insulin receptor (9-fold, p < 0.05), phosphoinositide 3-kinase (3-fold, p < 0.05), protein kinase B (4-fold, p < 0.05) phosphorylation and a decrease in insulin receptor substrate 1 serine phosphorylation induced increased glucose uptake (34%, p < 0.05) and glucose transporter 4 translocation (14-fold, p < 0.05) in CM-induced adipocytes. ConclusionsCocoa shell extract polyphenols reduced macrophages-adipocytes inflammatory interaction preventing mitochondrial dysfunction and insulin resistance. For the first time, cocoa shell aqueous extract showed a positive effect on adipogenesis and inflammation-related disorders. Funding SourcesUniversidad Autónoma de Madrid-Banco Santander, United States Department of Agriculture-National Institute of Food and Agriculture-HATCH, and the Spanish Ministry of Science and Innovation.