Dietary Blueberry Ameliorates Vascular Complications in Diabetic Mice Possibly through NOX4 and Modulates Composition and Functional Diversity of Gut Microbes.

Dietary Blueberry Ameliorates Vascular Complications in Diabetic Mice Possibly through NOX4 and Modulates Composition and Functional Diversity of Gut Microbes.
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DOI:
10.1002/mnfr.202100784
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发表时间:
2022-04
影响因子:
5.2
通讯作者:
Babu, Pon Velayutham Anandh
Babu, Pon Velayutham Anandh
中科院分区:
农林科学2区
文献类型:
--
作者:
Petersen, Chrissa;Bharat, Divya;Wankhade, Umesh D.;Kim, Ji-Seok;Cutler, Brett Ronald;Denetso, Christopher;Gholami, Samira;Nelson, Samantha;Bigley, Jessica;Johnson, Aspen;Chintapalli, Sree, V;Piccolo, Brian D.;Babu, Adhini Kuppuswamy Satheesh;Paz, Henry A.;Shankar, Kartik;Symons, J. David;Babu, Pon Velayutham Anandh

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In diabetes, endothelial inflammation and dysfunction plays a pivotal role in the development of vascular disease. We investigated the effect of dietary blueberries on vascular complications and gut microbiome in diabetic mice. Seven-week-old diabetic db/db mice consumed a standard diet (db/db) or a diet supplemented with 3.8% freeze-dried blueberry (db/db+BB) for 10 weeks. Control db/+ mice fed a standard diet (db/+). Vascular inflammation was assessed by measuring the monocyte binding to vasculature and inflammatory markers. Isometric tension procedures were used to assess mesenteric artery function. db/db mice exhibited enhanced vascular inflammation and reduced endothelial-dependent vasorelaxation as compared to db/+ mice but these were improved in db/db+BB mice. Blueberry supplementation reduced the expression of NOX4 and IκKβ in the aortic vessel and vascular endothelial cells (ECs) isolated from db/db+BB compared to db/db mice. The blueberry metabolites serum reduced glucose and palmitate induced endothelial inflammation in mouse aortic ECs. Further, blueberry supplementation increases commensal microbes and modulates the functional potential of gut microbes in diabetic mice. Dietary blueberry suppresses vascular inflammation, attenuates arterial endothelial dysfunction and supports the growth of commensal microbes in diabetic mice. The endothelial specific vascular benefits of blueberries are mediated through NOX4 signaling. Dietary supplementation of blueberry suppresses vascular inflammation, improves vascular dysfunction and increases the abundance of beneficial gut microbes in diabetic mice. The circulating metabolites of blueberry appears to exert benefits on the vascular endothelium. Our study provides strong proof of concept to consider blueberry supplementation as an adjunct therapy to lessen vascular complications in diabetes.
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