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Dietary Blueberry Attenuates Whole-Body Insulin Resistance in High Fat-Fed Mice by Reducing Adipocyte Death and Its Inflammatory Sequelae
Open accessAbstract
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.
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“This study also showed the protective effects of blueberries against insulin resistance and hyperglycemia, thus reducing the risk factors for CVD.”
From Berries: emerging impact on cardiovascular health (2010) · cites this paper as [64]
In the citing paper
“In an 8-week study, DeFuria et al. have shown the attenuation of inflammatory gene expressions in male C57Bl/6j mice fed a high-fat diet supplemented with blueberry powder versus the unsupplemented group.”
From Berries: emerging impact on cardiovascular health (2010) · cites this paper as [64]
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“Several lines of evidence indicate a role for berry anthocyanins in significantly decreasing oxidative damage and inflammation in cellular and animal models of CVD.”
From Berries: emerging impact on cardiovascular health (2010) · cites this paper as [64]
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“Increased adipocyte death in obesity is suggested (8) to reflect the elevated levels of cytotoxic stressors reported for obese AT (10,11,22).”
BackgroundFlavonoids: antioxidants or signalling molecules?
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Metadata
- Authors
- DeFuria, J., Bennett, G., Strissel, K. J., James, W. P., Milbury, P. E., Greenberg, A. S., & Obin, M. S.
- Affiliations
- Tufts University (US)
- Corresponding author
- James, W. Perfield
- Greenberg, Andrew S.
- Obin, Martin S.
- Venue
- The Journal of Nutrition
- Publisher
- Elsevier BV
- Published
- 2009-08
- Volume
- 139
- Issue
- 8
- Pages
- 1510-1516
- ISSN
- 0022-3166 (ISSN-L)
- PMC
- PMC2709302
- OpenAlex
- W2171102147
- Cited by
- 313
- References
- 36
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 14 · 2023: 8 · 2022: 12 · 2021: 27 · 2020: 15 · 2019: 22 · 2018: 19 · 2017: 23 · 2016: 19 · 2015: 22 · 2014: 24 · 2013: 33 · 2012: 16
- FWCI
- 13.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Nutrition (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- U.S. Department of Agriculture
- National Institutes of Health
- National Heart, Lung, and Blood Institute (TH32HL69772, T32HL069772)
- National Institute of Diabetes and Digestive and Kidney Diseases (T32DK062032)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
- Keywords
- blueberry, insulin resistance, adipose tissue inflammation, adipocyte death, high-fat diet, obesity, adipose tissue macrophages, oxidative stress, anthocyanins, M1 macrophage polarization, NF-κB signaling, MAPK signaling, hyperglycemia, dietary supplementation
- MeSH terms
- Animals, Anthocyanins, Anti-Inflammatory Agents, Diet, Dietary Fats, Fruit, Glutathione Peroxidase, Hyperglycemia, Insulin Resistance, Macrophages, Male, Mice, Inbred C57BL, Tumor Necrosis Factor-alpha, Signal Transduction, Interleukin-6, Gene Expression, Cell Death, Adipocytes, Chemokine CCL2, Plant Preparations, Blueberry Plants, Adiposity, Mice, Nitric Oxide Synthase Type II
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