Cocoa Shell Aqueous Phenolic Extract Preserves Mitochondrial Function and Insulin Sensitivity by Attenuating Inflammation between Macrophages and Adipocytes In Vitro.

Abstract

SCOPE\nThe aim is to assess the action of an aqueous extract from cocoa shell (CAE) and its main phenolic compounds to prevent the loss of obesity-induced mitochondrial function and insulin sensitivity, targeting inflammation between macrophages-adipocytes in vitro.\n\n\nMETHODS AND RESULTS\nCAE (31-500\xa0µg\xa0mL-1 ) inhibits 3T3-L1 adipocytes lipid accumulation and induces browning during differentiation. LPS-stimulated RAW264.7 macrophages show reduced inducible nitric oxide synthase and cyclooxygenase-2 expression and lowered pro-inflammatory cytokine production when treated with CAE and pure phenolics. Inflammatory crosstalk created by stimulating adipocytes with macrophage-conditioned media (CM) is arrested; CAE diminishes tumor necrosis factor-α (67%) and promotes adiponectin secretion (12.3-fold). Mitochondrial function, measured by reactive oxygen species production, mitochondrial content, and activity, is preserved in CM-treated adipocytes through up-regulating peroxisome proliferator-activated receptor gamma coactivator 1-α expression. Increases in insulin receptor (9-fold), phosphoinositide 3-kinase (3-fold), protein kinase B (4-fold) phosphorylation, and a decrease in insulin receptor substrate 1 serine phosphorylation induce increased glucose uptake (34%) and glucose transporter 4 translocation (14-fold) in CM-induced adipocytes.\n\n\nCONCLUSION\nCAE phenolics promote a beige phenotype in adipocytes. Macrophages-adipocytes inflammatory interaction is reduced preventing mitochondrial dysfunction and insulin resistance. For the first time, CAE shows a positive effect on adipogenesis and inflammation-related disorders.