Effects of Blueberry Supplementation on Glucose and Triacylglycerol Levels and Hepatic Oxidative Stress in Mice Fed a Western Diet

CMD and tested this hypothesis in a clinically relevant animal model of hypertension.Methods: Four-week-old female spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats were fed an open-source, compositionally defined control diet.After 24 weeks, SHRs were switched to a PBD (comprised of 28% fruits, vegetables, nuts and legumes), or maintained on the control diet for 12 more weeks (36 weeks total).Coronary flow reserve (CFR), a measure of microvascular function, was assessed via echocardiography at weeks 24 and 36.At week 36, hearts were excised for left ventricle protein analysis or VSMC isolation.Data were analyzed using one-way ANOVA or a t-test, depending on the comparison of interest.Results: At week 24, CFR was significantly greater in WKY (2.2 AE 0.3) compared to both groups of SHRs (1.6 AE 0.3 and 1.8 AE 0.2, P 0.002 and 0.04, for SHRs designated to the control and PBD diet, respectively), establishing that, as expected, CMD was present in both SHR groups (< 2 CFR).At week 36, SHR consuming PBD increased their CFR (+0.23 AE 0.2, P 0.02), while SHRs on the control diet had a nonsignificant decline in CFR (-0.17 AE 0.4, P 0.13).Left ventricular endothelial nitric oxide synthase phosphorylation (Ser1177), which improves endothelial function, was significantly increased in PBD-fed SHRs compared to control-fed SHRs (1.1 AE 0.1 vs 0.8 AE 0.1; P 0.01).Concomitantly, VSMCs isolated from SHRs exhibited a reduction in sodium nitroprussideinduced nitric oxide signaling via phosphorylation of vasodilatorstimulated phosphoprotein, which was preserved by PBD consumption (0.3 AE 0.1 vs 1.1 AE 0.8; P 0.03).Conclusions: A PBD reversed established CMD in SHRs.This was likely due to both endothelial-and VSMC-dependent mechanisms.Pilot clinical studies evaluating a PBD in CMD are warranted.