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

Mol Nutr Food Res. 2022 Apr;66(8):e2100784. doi: 10.1002/mnfr.202100784. Epub 2022 Feb 25.

Abstract

Scope: In diabetes, endothelial inflammation and dysfunction play a pivotal role in the development of vascular disease. This study investigates the effect of dietary blueberries on vascular complications and gut microbiome in diabetic mice.

Methods and results: Seven-week-old diabetic db/db mice consume a standard diet (db/db) or a diet supplemented with 3.8% freeze-dried blueberry (db/db+BB) for 10 weeks. Control db/+ mice are fed a standard diet (db/+). Vascular inflammation is assessed by measuring monocyte binding to vasculature and inflammatory markers. Isometric tension procedures are used to assess mesenteric artery function. db/db mice exhibit enhanced vascular inflammation and reduced endothelial-dependent vasorelaxation as compared to db/+ mice, but these are improved in db/db+BB mice. Blueberry supplementation reduces 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 reduces 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.

Conclusion: 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.

Keywords: blueberry; diabetes; endothelial dysfunction; endothelium; gut microbiota; metabolites; vascular disease; vascular inflammation.

MeSH terms

  • Animals
  • Blueberry Plants*
  • Diabetes Mellitus, Experimental* / diet therapy
  • Diabetes Mellitus, Experimental* / metabolism
  • Diabetes Mellitus, Experimental* / microbiology
  • Diabetes Mellitus, Type 2* / diet therapy
  • Diabetes Mellitus, Type 2* / metabolism
  • Diabetes Mellitus, Type 2* / microbiology
  • Diabetic Angiopathies* / diet therapy
  • Diabetic Angiopathies* / metabolism
  • Diabetic Angiopathies* / microbiology
  • Diet
  • Endothelial Cells / metabolism
  • Endothelium, Vascular
  • Gastrointestinal Microbiome* / drug effects
  • Inflammation / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • NADPH Oxidase 4* / metabolism

Substances

  • NADPH Oxidase 4
  • Nox4 protein, mouse