Dietary blueberry attenuates whole-body insulin resistance in high fat-fed mice by reducing adipocyte death and its inflammatory sequelae

J Nutr. 2009 Aug;139(8):1510-6. doi: 10.3945/jn.109.105155. Epub 2009 Jun 10.


Adipose tissue (AT) inflammation promotes insulin resistance (IR) and other obesity complications. AT inflammation and IR are associated with oxidative stress, adipocyte death, and the scavenging of dead adipocytes by proinflammatory CD11c+ AT macrophages (ATMPhi). We tested the hypothesis that supplementation of an obesitogenic (high-fat) diet with whole blueberry (BB) powder protects against AT inflammation and IR. Male C57Bl/6j mice were maintained for 8 wk on 1 of 3 diets: low-fat (10% of energy) diet (LFD), high-fat (60% of energy) diet (HFD) or the HFD containing 4% (wt:wt) whole BB powder (1:1 Vaccinium ashei and V. corymbosum) (HFD+B). BB supplementation (2.7% of total energy) did not affect HFD-associated alterations in energy intake, metabolic rate, body weight, or adiposity. We observed an emerging pattern of gene expression in AT of HFD mice indicating a shift toward global upregulation of inflammatory genes (tumor necrosis factor-alpha, interleukin-6, monocyte chemoattractant protein 1, inducible nitric oxide synthase), increased M1-polarized ATMPhi (CD11c+), and increased oxidative stress (reduced glutathione peroxidase 3). This shift was attenuated or nonexistent in HFD+B-fed mice. Furthermore, mice fed the HFD+B were protected from IR and hyperglycemia coincident with reductions in adipocyte death. Salutary effects of BB on adipocyte physiology and ATMPhi gene expression may reflect the ability of BB anthocyanins to alter mitogen-activated protein kinase and nuclear factor-kappaB stress signaling pathways, which regulate cell fate and inflammatory genes. These results suggest that cytoprotective and antiinflammatory actions of dietary BB can provide metabolic benefits to combat obesity-associated pathology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adipocytes / drug effects*
  • Adiposity / drug effects
  • Animals
  • Anthocyanins / pharmacology*
  • Anti-Inflammatory Agents / pharmacology*
  • Blueberry Plants* / chemistry
  • Cell Death / drug effects*
  • Cell Death / genetics
  • Chemokine CCL2 / metabolism
  • Diet
  • Dietary Fats / administration & dosage
  • Fruit
  • Gene Expression / drug effects
  • Glutathione Peroxidase / metabolism
  • Hyperglycemia / prevention & control
  • Insulin Resistance*
  • Interleukin-6 / metabolism
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nitric Oxide Synthase Type II / metabolism
  • Plant Preparations / chemistry
  • Plant Preparations / pharmacology*
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / metabolism


  • Anthocyanins
  • Anti-Inflammatory Agents
  • Chemokine CCL2
  • Dietary Fats
  • Interleukin-6
  • Plant Preparations
  • Tumor Necrosis Factor-alpha
  • Gpx3 protein, mouse
  • Glutathione Peroxidase
  • Nitric Oxide Synthase Type II