title: Anthocyanin increases adiponectin secretion and protects against diabetes-related endothelial dysfunction.
abstract: Adiponectin is an adipose tissue-secreted adipokine with beneficial effects on the cardiovascular system. In this study, we evaluated a potential role for adiponectin in the protective effects of anthocyanin on diabetes-related endothelial dysfunction. We treated db/db mice on a normal diet with anthocyanin cyanidin-3-O-β-glucoside (C3G; 2 g/kg diet) for 8 wk. Endothelium-dependent and -independent relaxations of the aorta were then evaluated. Adiponectin expression and secretion were also measured. C3G treatment restores endothelium-dependent relaxation of the aorta in db/db mice, whereas diabetic mice treated with an anti-adiponectin antibody do not respond. C3G treatment induces adiponectin expression and secretion in cultured 3T3 adipocytes through transcription factor forkhead box O1 (Foxo1). Silencing Foxo1 expression prevented C3G-stimulated induction of adiponectin expression. In contrast, overexpression of Foxo1-ADA promoted adiponectin expression in adipocytes. C3G activates Foxo1 by increasing its deacetylation via silent mating type information regulation 2 homolog 1 (Sirt1). Furthermore, purified anthocyanin supplementation significantly improved flow-mediated dilation (FMD) and increased serum adiponectin concentrations in patients with type 2 diabetes. Changes in adiponectin concentrations positively correlated with FMD in the anthocyanin group. Mechanistically, adiponectin activates cAMP-PKA-eNOS signaling pathways in human aortic endothelial cells, increasing endothelial nitric oxide bioavailability. These results demonstrate that adipocyte-derived adiponectin is required for anthocyanin C3G-mediated improvement of endothelial function in diabetes.
authors.affiliation: Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, Guangdong Province, China; and.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ruifang
authors.initials: R
authors.lastname: Sun
authors.forename: Min
authors.initials: M
authors.lastname: Xia
mesh_terms: D041721:3T3-L1 Cells; D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D000872:Anthocyanins / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D002478:Cells, Cultured; D019610:Cytoprotection; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D008297:Male; D051379:Mice; D051381:Rats
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D000872:Anthocyanins
keywords: adiponectin; anthocyanin; diabetes; endothelial function