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United States Department of Agriculture

Agricultural Research Service

Research Project: REGULATION OF ADIPOCYTE AND ADIPOSE TISSUE METABOLISM IN OBESITY RELATED INFLAMMATION AND METABOLIC DISORDERS Title: Dietary blueberry attenuates whole-body insulin resistance in high fat-fed mice by reducing adipocyte death and its inflammatory sequelae

Authors
item Defuria, Jason -
item Bennett, Grace -
item Strissel, Katherine -
item Milbury, Paul -
item Perfield, James -
item Greenberg, Andrew -
item Obin, Martin -

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: June 20, 2009
Publication Date: August 20, 2009
Citation: Defuria, J., Bennett, G., Strissel, K.J., Milbury, P.E., Perfield, J.W., Greenberg, A.S., Obin, M. 2009. Dietary blueberry attenuates whole-body insulin resistance in high fat-fed mice by reducing adipocyte death and its inflammatory sequelae. Journal of Nutrition. 139(8):1510-1516.

Interpretive Summary: In human and rodent obesity, adipose tissue (AT; fat tissue) inflammation promotes insulin resistance (IR), resulting in chronically high blood glucose levels (hyperglycemia). AT inflammation and IR are associated with events that promote immune cells of the body (macrophages) to enter obese adipose tissue and promote inflammation. As blueberries have been previously demonstrated to have anti-diabetic effects such as normalizing blood glucose levels in obesity, we tested the hypothesis that supplementation of a high-fat diet with whole blueberry (BB) powder protects against AT inflammation and IR. Male mice were maintained for 8 weeks on 1 of 3 diets: a low-fat diet (LFD), a high-fat diet (HFD) or a HFD containing 4% whole BB powder. BB supplementation did not affect HFD-associated changes in weight gain, fat or carbohydrate use, or inflammation. We observed an emerging pattern of gene expression in AT of HFD mice, indicating a change toward global upregulation of inflammatory genes known to be associated with insulin resistance. This change was blunted or nonexistent in HFD+B-fed mice. Furthermore, mice fed HFD+B were protected from IR and hyperglycemia, coincident with reductions in adipocyte death. Salutary effects of BB on adipocyte physiology and AT macrophages (ATMF) gene expression may reflect the ability of BB anthocyanins to alter protein cell signaling events important in the regulation of cell fate and inflammatory genes. These results suggest that cytoprotective and anti-inflammatory actions of dietary BB can provide metabolic benefits to combat obesity-associated pathology.

Technical Abstract: 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 (ATMF). 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 weeks on 1 of 3 diets: a low-fat (10% of energy) diet (LFD), a high-fat (60% of energy) diet (HFD) or a 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-a, interleukin-6, monocyte chemoattractant protein 1, inducible nitric oxide synthase), increased M1-polarized ATMF (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 ATMF gene expression may reflect the ability of BB anthocyanins to alter mitogen-activated protein kinase and nuclear factor-kB stress signaling pathways, which regulate cell fate and inflammatory genes. These results suggest that cytoprotective and anti-inflammatory actions of dietary BB can provide metabolic benefits to combat obesity-associated pathology.

Last Modified: 10/24/2014