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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]
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“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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Cani, P. D., Bibiloni, R., Knauf, C., Waget, A., Neyrinck, A. M., Delzenne, N. M., & Burcelin, R. (2008) · Diabetes · doi:10.2337/db07-1403 · Cited by 4,819
Obesity induces a phenotypic switch in adipose tissue macrophage polarization
Lumeng, C. N., Bodzin, J. L., & Saltiel, A. R. (2007) · Journal of Clinical Investigation · doi:10.1172/jci29881 · Cited by 4,664
Cinti, S., Mitchell, G., Barbatelli, G., Murano, I., Ceresi, E., Faloia, E., Wang, S., Fortier, M., Greenberg, A. S., & Obin, M. S. (2005) · Journal of Lipid Research · doi:10.1194/jlr.m500294-jlr200 · Cited by 2,529
Self-citationReactive oxygen species have a causal role in multiple forms of insulin resistance
Houstis, N., Rosen, E. D., & Lander, E. S. (2006) · Nature · doi:10.1038/nature04634 · Cited by 2,525 · cited 3×
“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?
Williams, R. J., Spencer, J. P. E., & Rice-Evans, C. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.01.001 · Cited by 2,016
Obesity, Inflammation, and Insulin Resistance
Shoelson, S. E., Herrero, L., & Naaz, A. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.03.059 · Cited by 1,806
IKK-β links inflammation to obesity-induced insulin resistance
Arkan, M. C., Hevener, A. L., Greten, F. R., Maeda, S., Li, Z.-W., Long, J. M., Wynshaw-Boris, A., Poli, G., Olefsky, J., & Karin, M. (2005) · Nature Medicine · doi:10.1038/nm1185 · Cited by 1,773
Lumeng, C. N., DeYoung, S. M., Bodzin, J. L., & Saltiel, A. R. (2007) · Diabetes · doi:10.2337/db06-1076 · Cited by 1,016
Adipocyte Death, Adipose Tissue Remodeling, and Obesity Complications
Strissel, K. J., Stancheva, Z., Miyoshi, H., Perfield, J. W., DeFuria, J., Jick, Z., Greenberg, A. S., & Obin, M. S. (2007) · Diabetes · doi:10.2337/db07-0767 · Cited by 1,007
Self-citationLumeng, C. N.-K., DelProposto, J. B., Westcott, D. J., & Saltiel, A. R. (2008) · Diabetes · doi:10.2337/db08-0872 · Cited by 956
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Hanhineva, K., Törrönen, R., Bondia‐Pons, I., Pekkinen, J., Kolehmainen, M., Mykkänen, H. M., & Poutanen, K. S. (2010) · International Journal of Molecular Sciences · doi:10.3390/ijms11041365 · Cited by 1,203
Recent Research on the Health Benefits of Blueberries and Their Anthocyanins
Kalt, W., Cassidy, A., Howard, L. R., Krikorian, R., Stull, A. J., Tremblay, F., & Zamora‐Ros, R. (2019) · Advances in Nutrition · doi:10.1093/advances/nmz065 · Cited by 705
The Case for Anthocyanin Consumption to Promote Human Health: A Review
Pojer, E., Mattivi, F., Johnson, D., & Stockley, C. S. (2013) · Comprehensive Reviews in Food Science and Food Safety · doi:10.1111/1541-4337.12024 · Cited by 657
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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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