Cyanidin-3-O-β-Glucoside and Protocatechuic Acid Exert Insulin-Like Effects by Upregulating PPARγ Activity in Human Omental Adipocytes

Insulin resistance (IR) represents an independent risk factor for metabolic, cardiovascular, and neoplastic disorders. Preventing/attenuating IR is a major objective to be reached to preserve population health. Because many insulin-sensitizing drugs have shown unwanted side effects, active harmless compounds are sought after. Dietary anthocyanins have been demonstrated to ameliorate hyperglycemia and insulin sensitivity. This study aimed at investigating whether cyanidin-3-O-β-glucoside (C3G) and its metabolite protocatechuic acid (PCA) might have a role in glucose transport activation in human omental adipocytes and 3T3-L1 cells. In cells treated with 50 µmol/L C3G and 100 µmol/L PCA, [(3)H]-2-deoxyglucose uptake, GLUT4 translocation by immunoblotting, adiponectin secretion, and peroxisome proliferator-activated receptor-γ (PPARγ) activation by enzyme-linked immunosorbent assay kits were evaluated. Parallel experiments were carried out in murine adipocyte 3T3-L1. To define the role of PPARγ in modulating polyphenol effects, small interfering RNA technique and PPARγ antagonist were used to inhibit transcription factor activity. C3G and PCA increased adipocyte glucose uptake (P < 0.05) and GLUT4 membrane translocation (P < 0.01). Significant increases (P < 0.05) in nuclear PPARγ activity, as well as in adiponectin and GLUT4 expressions (P < 0.01), were also shown. It is interesting that PPARγ inhibition counteracted the polyphenol-induced adiponectin and GLUT4 upregulations, suggesting a direct involvement of PPARγ in this process. Our study provides evidence that C3G and PCA might exert insulin-like activities by PPARγ activation, evidencing a causal relationship between this transcription factor and adiponectin and GLUT4 upregulation. Dietary polyphenols could be included in the preventive/therapeutic armory against pathological conditions associated with IR.