Blueberry Metabolites Attenuate Lipotoxicity‐Induced Endothelial Dysfunction

• Published in: Molecular nutrition & food research 2018-01, Vol.62 (2), p.n/a
• Main Authors: Bharat, Divya, Cavalcanti, Rafaela Ramos Mororo, Petersen, Chrissa, Begaye, Nathan, Cutler, Brett Ronald, Costa, Marcella Melo Assis, Ramos, Renata Kelly Luna Gomes, Ferreira, Marina Ramos, Li, Youyou, Bharath, Leena P., Toolson, Emma, Sebahar, Paul, Looper, Ryan E., Jalili, Thunder, Rajasekaran, Namakkal S., Jia, Zhenquan, Symons, J. David, Anandh Babu, Pon Velayutham
• Format: Article
• Language: English
• Subjects: Animals; Anthocyanins; Anthocyanins - pharmacology; Aorta - cytology; Benzoic acid; Blueberries; blueberry metabolites; Blueberry Plants - chemistry; Blueberry Plants - metabolism; Cells, Cultured; Chemokines; Diabetes mellitus; Endothelial Cells; endothelial dysfunction; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Endothelium, Vascular - physiopathology; Fruits; Gene expression; Gene Expression Regulation - drug effects; Hippuric acid; Humans; inflammation; Insulin - pharmacology; Male; Metabolites; Mice, Inbred C57BL; Monocytes; Nitric oxide; Nitric Oxide - metabolism; NOX4 protein; Palmitic acid; Palmitic Acid - toxicity; Reactive oxygen species; Reactive Oxygen Species - metabolism; Sulfates; Vaccinium; Vanillic acid; vascular effects
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201700601

Scope Lipotoxicity‐induced endothelial dysfunction is an important vascular complication associated with diabetes. Clinical studies support the vascular benefits of blueberry anthocyanins, but the underlying mechanism is unclear. The hypothesis that metabolites of blueberry anthocyanins attenuate lipotoxicity‐induced endothelial dysfunction was tested. Methods and results Human aortic endothelial cells (HAECs) were treated for 6 h with either: (i) the parent anthocyanins (malvidin‐3‐glucoside and cyanidin‐3‐glucoside); or (ii) the blueberry metabolites (hydroxyhippuric acid, hippuric acid, benzoic acid‐4‐sulfate, isovanillic acid‐3‐sulfate, and vanillic acid‐4‐sulfate), at concentrations known to circulate in humans following blueberry consumption. For the last 5 h HAECs were treated with palmitate or vehicle. HAECs treated with palmitate displayed elevated reactive oxygen species generation, increased mRNA expression of NOX4, chemokines, adhesion molecules, and IκBα, exaggerated monocyte binding, and suppressed nitric oxide production. Of note, the damaging effects of palmitate were ameliorated in HAECs treated with blueberry metabolites but not parent anthocyanins. Further, important translational relevance of these results was provided by our observation that palmitate‐induced endothelial dysfunction was lessened in arterial segments that incubated concurrently with blueberry metabolites. Conclusion The presented findings indicate that the vascular benefits of blueberry anthocyanins are mediated by their metabolites. Blueberries might complement existing therapies to lessen vascular complications. Blueberry metabolites lessen indices of lipotoxicity‐induced oxidant stress, inflammation, monocyte adhesion, and endothelial dysfunction.