Blueberry Metabolites Attenuate Lipotoxicity-Induced Endothelial Dysfunction.

Bharat D1, Cavalcanti RRM1, Petersen C1, Begaye N1, Cutler BR1, Costa MMA1, Ramos RKLG1, Ferreira MR1, Li Y1, Bharath LP1, Toolson E1, Sebahar P2, Looper RE2, Jalili T1, Rajasekaran NS3, Jia Z4, Symons JD1,5, Anandh Babu PV1
Source: Mol Nutr Food Res
Publication Date: (2018)
Issue: 62:
Cells used in publication:
Endothelial, aortic, human (HAEC)
Species: human
Tissue Origin: aortic



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.


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 I?Ba, 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.


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