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

Adipose tissue (AT) inflammation promotes insulin resistance (I R) and other obesity complications. AT inflammation and I R are associated with oxidative stress, adipocyte death, and the scavenging of dead adipocytes by proinflammatory CD11 c+ AT macrophages (ATM[PHI]). We tested the hypothesis that supplementation of an obesitogenic (high-fat) diet with whole blueberry (BB) powder protects against AT inflammation and IR. Male C57BI/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-e, interleukin-6, monocyte chemoattractant protein 1, inducible nitric oxide synthase), increased Ml-polarized ATM[PHI] (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 ATM[PHI] gene expression may reflect the ability of BB anthocyanins to alter mitogen-activated protein kinase and nuclear factor-[kappa]B 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. J. Nutr. 139:1510-1516, 2009.