A blueberry-enriched diet improves renal function and reduces oxidative stress in metabolic syndrome animals: potential mechanism of TLR4-MAPK signaling pathway
Anand R Nair, Carrie M Elks, Jorge Vila, Fabio Del Piero, Daniel B Paulsen, Joseph Francis, Anand R Nair, Carrie M Elks, Jorge Vila, Fabio Del Piero, Daniel B Paulsen, Joseph Francis
Abstract
Background: Metabolic syndrome (MetS) is characterized by a cluster of health factors that indicate a higher risk for cardio-renal diseases. Recent evidence indicates that antioxidants from berries are alternative to attenuate oxidative stress and inflammation. We tested the hypothesis that inflammation-induced renal damage is triggered by the activation of TLR4, and subsequent modulation of redox-sensitive molecules and mitogen-activated protein kinase (MAPK) pathway.
Methods: Five-week old lean and obese Zucker rats (LZR and OZR) were fed a blueberry-enriched diet or an isocaloric control diet for 15 weeks. A glucose tolerance test and acute renal clearance experiments were performed. Gene and protein expression levels for TLR4, cytokines and phosphorylation of ERK and p38MAPK were measured. Kidney redox status and urinary albumin levels were quantified. Renal pathology was evaluated histologically.
Results: Control OZR exhibited lower glucose tolerance; exacerbated renal function parameters; increased oxidative stress. Gene and protein expression levels of TLR4 were higher and this was accompanied by increased renal pathology with extensive albuminuria and deterioration in antioxidant levels in OZR. In addition, OZR had increased phosphorylation of ERK and p38MAPK. Blueberry-fed OZR exhibited significant improvements in all these parameters compared to OZR.
Conclusion: TLR4-MAPK signaling pathway is a key to the renal structural injury and dysfunction in MetS and blueberry (BB) protect against this damage by inhibiting TLR4.
Significance: This is the first study to put forth a potential mechanism of TLR4-induced kidney damage in a model of MetS and to elucidate a downstream mechanism by which blueberry exert their reno-protective effects.
Conflict of interest statement
Competing Interests: The authors have declared that no competing interests exist.
Figures
![Figure 1. Effect of BB feeding on…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4221362/bin/pone.0111976.g001.jpg)
Figure 2. Effect of BB on renal…
Figure 2. Effect of BB on renal hemodynamic dysfunctions in MetS animals.
The kidney function…
Figure 3. Effect of BB on renal…
Figure 3. Effect of BB on renal renin-angiotensin system in MetS animals.
The mRNA expression…
Figure 4. Effect of BB on renal…
Figure 4. Effect of BB on renal pathology in MetS animals.
(A) Representative images of…
Figure 5. Effect of BB on renal…
Figure 5. Effect of BB on renal pathology in MetS animals (pathological scoring).
(A) Relative…
Figure 6. Effect of BB on renal…
Figure 6. Effect of BB on renal TLR4 gene and protein expression in MetS animals.
Figure 7. Effect of BB on MAPK…
Figure 7. Effect of BB on MAPK signaling in MetS animals.
The protein expression of…
Figure 8. Effect of BB on the…
Figure 8. Effect of BB on the renal inflammatory profile in MetS animals.
The (A)…
Figure 9. Effects of BB on antioxidant…
Figure 9. Effects of BB on antioxidant enzymes and Nrf2-Keap1 signaling in MetS animals.
Renal…
- Wild blueberry (Vaccinium angustifolium) consumption improves inflammatory status in the obese Zucker rat model of the metabolic syndrome.Vendrame S, Daugherty A, Kristo AS, Riso P, Klimis-Zacas D. Vendrame S, et al. J Nutr Biochem. 2013 Aug;24(8):1508-12. doi: 10.1016/j.jnutbio.2012.12.010. Epub 2013 Mar 1. J Nutr Biochem. 2013. PMID: 23465589
- Diet-induced renal changes in Zucker rats are ameliorated by the superoxide dismutase mimetic TEMPOL.Ebenezer PJ, Mariappan N, Elks CM, Haque M, Francis J. Ebenezer PJ, et al. Obesity (Silver Spring). 2009 Nov;17(11):1994-2002. doi: 10.1038/oby.2009.137. Epub 2009 May 7. Obesity (Silver Spring). 2009. PMID: 19424163 Free PMC article.
- Nitric oxide activates PI3-K and MAPK signalling pathways in human and rat vascular smooth muscle cells: influence of insulin resistance and oxidative stress.Doronzo G, Viretto M, Russo I, Mattiello L, Di Martino L, Cavalot F, Anfossi G, Trovati M. Doronzo G, et al. Atherosclerosis. 2011 May;216(1):44-53. doi: 10.1016/j.atherosclerosis.2011.01.019. Epub 2011 Jan 21. Atherosclerosis. 2011. PMID: 21316056
- A blueberry-enriched diet attenuates nephropathy in a rat model of hypertension via reduction in oxidative stress.Elks CM, Reed SD, Mariappan N, Shukitt-Hale B, Joseph JA, Ingram DK, Francis J. Elks CM, et al. PLoS One. 2011;6(9):e24028. doi: 10.1371/journal.pone.0024028. Epub 2011 Sep 15. PLoS One. 2011. PMID: 21949690 Free PMC article.
- Berries as a Treatment for Obesity-Induced Inflammation: Evidence from Preclinical Models.Land Lail H, Feresin RG, Hicks D, Stone B, Price E, Wanders D. Land Lail H, et al. Nutrients. 2021 Jan 23;13(2):334. doi: 10.3390/nu13020334. Nutrients. 2021. PMID: 33498671 Free PMC article. Review.
- Association between Consumption of Dietary Supplements and Chronic Kidney Disease Prevalence: Results of the Korean Nationwide Population-Based Survey.Fang Y, Lee H, Son S, Oh S, Jo SK, Cho W, Kim MG. Fang Y, et al. Nutrients. 2023 Feb 5;15(4):822. doi: 10.3390/nu15040822. Nutrients. 2023. PMID: 36839180 Free PMC article.
- Blueberry Consumption and Changes in Obesity and Diabetes Mellitus Outcomes: A Systematic Review.de Oliveira MS, Pellenz FM, de Souza BM, Crispim D. de Oliveira MS, et al. Metabolites. 2022 Dec 22;13(1):19. doi: 10.3390/metabo13010019. Metabolites. 2022. PMID: 36676944 Free PMC article. Review.
- Activation of angiotensin-converting enzyme 2 ameliorates metabolic syndrome-induced renal damage in rats by renal TLR4 and nuclear transcription factor κB downregulation.El-Domiaty HF, Sweed E, Kora MA, Zaki NG, Khodir SA. El-Domiaty HF, et al. Front Med (Lausanne). 2022 Aug 12;9:904756. doi: 10.3389/fmed.2022.904756. eCollection 2022. Front Med (Lausanne). 2022. PMID: 36035416 Free PMC article.
- Blueberry Supplementation in Midlife for Dementia Risk Reduction.Krikorian R, Skelton MR, Summer SS, Shidler MD, Sullivan PG. Krikorian R, et al. Nutrients. 2022 Apr 13;14(8):1619. doi: 10.3390/nu14081619. Nutrients. 2022. PMID: 35458181 Free PMC article. Clinical Trial.
- Blueberry as an Attractive Functional Fruit to Prevent (Pre)Diabetes Progression.Nunes S, Vieira P, Gomes P, Viana SD, Reis F. Nunes S, et al. Antioxidants (Basel). 2021 Jul 22;10(8):1162. doi: 10.3390/antiox10081162. Antioxidants (Basel). 2021. PMID: 34439410 Free PMC article. Review.
-
- Ervin RB (2009) Prevalence of metabolic syndrome among adults 20 years of age and over, by sex, age, race and ethnicity, and body mass index: United States, 2003–2006. Natl Health Stat Report: 1–7. - PubMed
-
- Elks CM, Francis J, Stull AJ, Cefalu WT, Shukitt-Hale B, et al... (2013) Overview of the Health Properties of Blueberries. In: Hunter MSaD, editor. Bioactives in Fruit: Health Benefits and Functional Foods Oxford, UK: John Wiley & Sons, Ltd. doi:10.1002/9781118635551.ch11.
- Animals
- Blueberry Plants / chemistry*
- Body Weight
- Diet*
- Disease Models, Animal
- Extracellular Signal-Regulated MAP Kinases / metabolism
- Gene Expression
- Glucose / metabolism
- Hemodynamics
- Kidney / metabolism*
- Kidney / pathology
- Kidney / physiopathology
- Kidney Function Tests
- Kidney Glomerulus / metabolism
- Kidney Glomerulus / pathology
- Male
- Metabolic Syndrome / genetics
- Metabolic Syndrome / metabolism*
- Metabolic Syndrome / physiopathology
- Mice, Knockout
- Mitogen-Activated Protein Kinases / metabolism
- NF-kappa B / metabolism
- Oxidation-Reduction
- Oxidative Stress*
- Phosphorylation
- Rats
- Toll-Like Receptor 4 / genetics
- Toll-Like Receptor 4 / metabolism
- p38 Mitogen-Activated Protein Kinases
- NF-kappa B
- Toll-Like Receptor 4
- Extracellular Signal-Regulated MAP Kinases
- Mitogen-Activated Protein Kinases
- p38 Mitogen-Activated Protein Kinases
- Glucose
- Full Text Sources
- Other Literature Sources
- Medical
- Miscellaneous
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Figure 2. Effect of BB on renal…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4221362/bin/pone.0111976.g002.jpg)
Figure 3. Effect of BB on renal…
Figure 3. Effect of BB on renal renin-angiotensin system in MetS animals.
The mRNA expression…
Figure 4. Effect of BB on renal…
Figure 4. Effect of BB on renal pathology in MetS animals.
(A) Representative images of…
Figure 5. Effect of BB on renal…
Figure 5. Effect of BB on renal pathology in MetS animals (pathological scoring).
(A) Relative…
Figure 6. Effect of BB on renal…
Figure 6. Effect of BB on renal TLR4 gene and protein expression in MetS animals.
Figure 7. Effect of BB on MAPK…
Figure 7. Effect of BB on MAPK signaling in MetS animals.
The protein expression of…
Figure 8. Effect of BB on the…
Figure 8. Effect of BB on the renal inflammatory profile in MetS animals.
The (A)…
Figure 9. Effects of BB on antioxidant…
Figure 9. Effects of BB on antioxidant enzymes and Nrf2-Keap1 signaling in MetS animals.
Renal…
- Wild blueberry (Vaccinium angustifolium) consumption improves inflammatory status in the obese Zucker rat model of the metabolic syndrome.Vendrame S, Daugherty A, Kristo AS, Riso P, Klimis-Zacas D. Vendrame S, et al. J Nutr Biochem. 2013 Aug;24(8):1508-12. doi: 10.1016/j.jnutbio.2012.12.010. Epub 2013 Mar 1. J Nutr Biochem. 2013. PMID: 23465589
- Diet-induced renal changes in Zucker rats are ameliorated by the superoxide dismutase mimetic TEMPOL.Ebenezer PJ, Mariappan N, Elks CM, Haque M, Francis J. Ebenezer PJ, et al. Obesity (Silver Spring). 2009 Nov;17(11):1994-2002. doi: 10.1038/oby.2009.137. Epub 2009 May 7. Obesity (Silver Spring). 2009. PMID: 19424163 Free PMC article.
- Nitric oxide activates PI3-K and MAPK signalling pathways in human and rat vascular smooth muscle cells: influence of insulin resistance and oxidative stress.Doronzo G, Viretto M, Russo I, Mattiello L, Di Martino L, Cavalot F, Anfossi G, Trovati M. Doronzo G, et al. Atherosclerosis. 2011 May;216(1):44-53. doi: 10.1016/j.atherosclerosis.2011.01.019. Epub 2011 Jan 21. Atherosclerosis. 2011. PMID: 21316056
- A blueberry-enriched diet attenuates nephropathy in a rat model of hypertension via reduction in oxidative stress.Elks CM, Reed SD, Mariappan N, Shukitt-Hale B, Joseph JA, Ingram DK, Francis J. Elks CM, et al. PLoS One. 2011;6(9):e24028. doi: 10.1371/journal.pone.0024028. Epub 2011 Sep 15. PLoS One. 2011. PMID: 21949690 Free PMC article.
- Berries as a Treatment for Obesity-Induced Inflammation: Evidence from Preclinical Models.Land Lail H, Feresin RG, Hicks D, Stone B, Price E, Wanders D. Land Lail H, et al. Nutrients. 2021 Jan 23;13(2):334. doi: 10.3390/nu13020334. Nutrients. 2021. PMID: 33498671 Free PMC article. Review.
- Association between Consumption of Dietary Supplements and Chronic Kidney Disease Prevalence: Results of the Korean Nationwide Population-Based Survey.Fang Y, Lee H, Son S, Oh S, Jo SK, Cho W, Kim MG. Fang Y, et al. Nutrients. 2023 Feb 5;15(4):822. doi: 10.3390/nu15040822. Nutrients. 2023. PMID: 36839180 Free PMC article.
- Blueberry Consumption and Changes in Obesity and Diabetes Mellitus Outcomes: A Systematic Review.de Oliveira MS, Pellenz FM, de Souza BM, Crispim D. de Oliveira MS, et al. Metabolites. 2022 Dec 22;13(1):19. doi: 10.3390/metabo13010019. Metabolites. 2022. PMID: 36676944 Free PMC article. Review.
- Activation of angiotensin-converting enzyme 2 ameliorates metabolic syndrome-induced renal damage in rats by renal TLR4 and nuclear transcription factor κB downregulation.El-Domiaty HF, Sweed E, Kora MA, Zaki NG, Khodir SA. El-Domiaty HF, et al. Front Med (Lausanne). 2022 Aug 12;9:904756. doi: 10.3389/fmed.2022.904756. eCollection 2022. Front Med (Lausanne). 2022. PMID: 36035416 Free PMC article.
- Blueberry Supplementation in Midlife for Dementia Risk Reduction.Krikorian R, Skelton MR, Summer SS, Shidler MD, Sullivan PG. Krikorian R, et al. Nutrients. 2022 Apr 13;14(8):1619. doi: 10.3390/nu14081619. Nutrients. 2022. PMID: 35458181 Free PMC article. Clinical Trial.
- Blueberry as an Attractive Functional Fruit to Prevent (Pre)Diabetes Progression.Nunes S, Vieira P, Gomes P, Viana SD, Reis F. Nunes S, et al. Antioxidants (Basel). 2021 Jul 22;10(8):1162. doi: 10.3390/antiox10081162. Antioxidants (Basel). 2021. PMID: 34439410 Free PMC article. Review.
-
- Ervin RB (2009) Prevalence of metabolic syndrome among adults 20 years of age and over, by sex, age, race and ethnicity, and body mass index: United States, 2003–2006. Natl Health Stat Report: 1–7. - PubMed
-
- Elks CM, Francis J, Stull AJ, Cefalu WT, Shukitt-Hale B, et al... (2013) Overview of the Health Properties of Blueberries. In: Hunter MSaD, editor. Bioactives in Fruit: Health Benefits and Functional Foods Oxford, UK: John Wiley & Sons, Ltd. doi:10.1002/9781118635551.ch11.
- Animals
- Blueberry Plants / chemistry*
- Body Weight
- Diet*
- Disease Models, Animal
- Extracellular Signal-Regulated MAP Kinases / metabolism
- Gene Expression
- Glucose / metabolism
- Hemodynamics
- Kidney / metabolism*
- Kidney / pathology
- Kidney / physiopathology
- Kidney Function Tests
- Kidney Glomerulus / metabolism
- Kidney Glomerulus / pathology
- Male
- Metabolic Syndrome / genetics
- Metabolic Syndrome / metabolism*
- Metabolic Syndrome / physiopathology
- Mice, Knockout
- Mitogen-Activated Protein Kinases / metabolism
- NF-kappa B / metabolism
- Oxidation-Reduction
- Oxidative Stress*
- Phosphorylation
- Rats
- Toll-Like Receptor 4 / genetics
- Toll-Like Receptor 4 / metabolism
- p38 Mitogen-Activated Protein Kinases
- NF-kappa B
- Toll-Like Receptor 4
- Extracellular Signal-Regulated MAP Kinases
- Mitogen-Activated Protein Kinases
- p38 Mitogen-Activated Protein Kinases
- Glucose
- Full Text Sources
- Other Literature Sources
- Medical
- Miscellaneous
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Figure 3. Effect of BB on renal…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4221362/bin/pone.0111976.g003.jpg)
Figure 4. Effect of BB on renal…
Figure 4. Effect of BB on renal pathology in MetS animals.
(A) Representative images of…
Figure 5. Effect of BB on renal…
Figure 5. Effect of BB on renal pathology in MetS animals (pathological scoring).
(A) Relative…
Figure 6. Effect of BB on renal…
Figure 6. Effect of BB on renal TLR4 gene and protein expression in MetS animals.
Figure 7. Effect of BB on MAPK…
Figure 7. Effect of BB on MAPK signaling in MetS animals.
The protein expression of…
Figure 8. Effect of BB on the…
Figure 8. Effect of BB on the renal inflammatory profile in MetS animals.
The (A)…
Figure 9. Effects of BB on antioxidant…
Figure 9. Effects of BB on antioxidant enzymes and Nrf2-Keap1 signaling in MetS animals.
Renal…
- Wild blueberry (Vaccinium angustifolium) consumption improves inflammatory status in the obese Zucker rat model of the metabolic syndrome.Vendrame S, Daugherty A, Kristo AS, Riso P, Klimis-Zacas D. Vendrame S, et al. J Nutr Biochem. 2013 Aug;24(8):1508-12. doi: 10.1016/j.jnutbio.2012.12.010. Epub 2013 Mar 1. J Nutr Biochem. 2013. PMID: 23465589
- Diet-induced renal changes in Zucker rats are ameliorated by the superoxide dismutase mimetic TEMPOL.Ebenezer PJ, Mariappan N, Elks CM, Haque M, Francis J. Ebenezer PJ, et al. Obesity (Silver Spring). 2009 Nov;17(11):1994-2002. doi: 10.1038/oby.2009.137. Epub 2009 May 7. Obesity (Silver Spring). 2009. PMID: 19424163 Free PMC article.
- Nitric oxide activates PI3-K and MAPK signalling pathways in human and rat vascular smooth muscle cells: influence of insulin resistance and oxidative stress.Doronzo G, Viretto M, Russo I, Mattiello L, Di Martino L, Cavalot F, Anfossi G, Trovati M. Doronzo G, et al. Atherosclerosis. 2011 May;216(1):44-53. doi: 10.1016/j.atherosclerosis.2011.01.019. Epub 2011 Jan 21. Atherosclerosis. 2011. PMID: 21316056
- A blueberry-enriched diet attenuates nephropathy in a rat model of hypertension via reduction in oxidative stress.Elks CM, Reed SD, Mariappan N, Shukitt-Hale B, Joseph JA, Ingram DK, Francis J. Elks CM, et al. PLoS One. 2011;6(9):e24028. doi: 10.1371/journal.pone.0024028. Epub 2011 Sep 15. PLoS One. 2011. PMID: 21949690 Free PMC article.
- Berries as a Treatment for Obesity-Induced Inflammation: Evidence from Preclinical Models.Land Lail H, Feresin RG, Hicks D, Stone B, Price E, Wanders D. Land Lail H, et al. Nutrients. 2021 Jan 23;13(2):334. doi: 10.3390/nu13020334. Nutrients. 2021. PMID: 33498671 Free PMC article. Review.
- Association between Consumption of Dietary Supplements and Chronic Kidney Disease Prevalence: Results of the Korean Nationwide Population-Based Survey.Fang Y, Lee H, Son S, Oh S, Jo SK, Cho W, Kim MG. Fang Y, et al. Nutrients. 2023 Feb 5;15(4):822. doi: 10.3390/nu15040822. Nutrients. 2023. PMID: 36839180 Free PMC article.
- Blueberry Consumption and Changes in Obesity and Diabetes Mellitus Outcomes: A Systematic Review.de Oliveira MS, Pellenz FM, de Souza BM, Crispim D. de Oliveira MS, et al. Metabolites. 2022 Dec 22;13(1):19. doi: 10.3390/metabo13010019. Metabolites. 2022. PMID: 36676944 Free PMC article. Review.
- Activation of angiotensin-converting enzyme 2 ameliorates metabolic syndrome-induced renal damage in rats by renal TLR4 and nuclear transcription factor κB downregulation.El-Domiaty HF, Sweed E, Kora MA, Zaki NG, Khodir SA. El-Domiaty HF, et al. Front Med (Lausanne). 2022 Aug 12;9:904756. doi: 10.3389/fmed.2022.904756. eCollection 2022. Front Med (Lausanne). 2022. PMID: 36035416 Free PMC article.
- Blueberry Supplementation in Midlife for Dementia Risk Reduction.Krikorian R, Skelton MR, Summer SS, Shidler MD, Sullivan PG. Krikorian R, et al. Nutrients. 2022 Apr 13;14(8):1619. doi: 10.3390/nu14081619. Nutrients. 2022. PMID: 35458181 Free PMC article. Clinical Trial.
- Blueberry as an Attractive Functional Fruit to Prevent (Pre)Diabetes Progression.Nunes S, Vieira P, Gomes P, Viana SD, Reis F. Nunes S, et al. Antioxidants (Basel). 2021 Jul 22;10(8):1162. doi: 10.3390/antiox10081162. Antioxidants (Basel). 2021. PMID: 34439410 Free PMC article. Review.
-
- Ervin RB (2009) Prevalence of metabolic syndrome among adults 20 years of age and over, by sex, age, race and ethnicity, and body mass index: United States, 2003–2006. Natl Health Stat Report: 1–7. - PubMed
-
- Elks CM, Francis J, Stull AJ, Cefalu WT, Shukitt-Hale B, et al... (2013) Overview of the Health Properties of Blueberries. In: Hunter MSaD, editor. Bioactives in Fruit: Health Benefits and Functional Foods Oxford, UK: John Wiley & Sons, Ltd. doi:10.1002/9781118635551.ch11.
- Animals
- Blueberry Plants / chemistry*
- Body Weight
- Diet*
- Disease Models, Animal
- Extracellular Signal-Regulated MAP Kinases / metabolism
- Gene Expression
- Glucose / metabolism
- Hemodynamics
- Kidney / metabolism*
- Kidney / pathology
- Kidney / physiopathology
- Kidney Function Tests
- Kidney Glomerulus / metabolism
- Kidney Glomerulus / pathology
- Male
- Metabolic Syndrome / genetics
- Metabolic Syndrome / metabolism*
- Metabolic Syndrome / physiopathology
- Mice, Knockout
- Mitogen-Activated Protein Kinases / metabolism
- NF-kappa B / metabolism
- Oxidation-Reduction
- Oxidative Stress*
- Phosphorylation
- Rats
- Toll-Like Receptor 4 / genetics
- Toll-Like Receptor 4 / metabolism
- p38 Mitogen-Activated Protein Kinases
- NF-kappa B
- Toll-Like Receptor 4
- Extracellular Signal-Regulated MAP Kinases
- Mitogen-Activated Protein Kinases
- p38 Mitogen-Activated Protein Kinases
- Glucose
- Full Text Sources
- Other Literature Sources
- Medical
- Miscellaneous
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Figure 4. Effect of BB on renal…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4221362/bin/pone.0111976.g004.jpg)
![Figure 5. Effect of BB on renal…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4221362/bin/pone.0111976.g005.jpg)
![Figure 6. Effect of BB on renal…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4221362/bin/pone.0111976.g006.jpg)
Figure 7. Effect of BB on MAPK…
Figure 7. Effect of BB on MAPK signaling in MetS animals.
The protein expression of…
Figure 8. Effect of BB on the…
Figure 8. Effect of BB on the renal inflammatory profile in MetS animals.
The (A)…
Figure 9. Effects of BB on antioxidant…
Figure 9. Effects of BB on antioxidant enzymes and Nrf2-Keap1 signaling in MetS animals.
Renal…
- Wild blueberry (Vaccinium angustifolium) consumption improves inflammatory status in the obese Zucker rat model of the metabolic syndrome.Vendrame S, Daugherty A, Kristo AS, Riso P, Klimis-Zacas D. Vendrame S, et al. J Nutr Biochem. 2013 Aug;24(8):1508-12. doi: 10.1016/j.jnutbio.2012.12.010. Epub 2013 Mar 1. J Nutr Biochem. 2013. PMID: 23465589
- Diet-induced renal changes in Zucker rats are ameliorated by the superoxide dismutase mimetic TEMPOL.Ebenezer PJ, Mariappan N, Elks CM, Haque M, Francis J. Ebenezer PJ, et al. Obesity (Silver Spring). 2009 Nov;17(11):1994-2002. doi: 10.1038/oby.2009.137. Epub 2009 May 7. Obesity (Silver Spring). 2009. PMID: 19424163 Free PMC article.
- Nitric oxide activates PI3-K and MAPK signalling pathways in human and rat vascular smooth muscle cells: influence of insulin resistance and oxidative stress.Doronzo G, Viretto M, Russo I, Mattiello L, Di Martino L, Cavalot F, Anfossi G, Trovati M. Doronzo G, et al. Atherosclerosis. 2011 May;216(1):44-53. doi: 10.1016/j.atherosclerosis.2011.01.019. Epub 2011 Jan 21. Atherosclerosis. 2011. PMID: 21316056
- A blueberry-enriched diet attenuates nephropathy in a rat model of hypertension via reduction in oxidative stress.Elks CM, Reed SD, Mariappan N, Shukitt-Hale B, Joseph JA, Ingram DK, Francis J. Elks CM, et al. PLoS One. 2011;6(9):e24028. doi: 10.1371/journal.pone.0024028. Epub 2011 Sep 15. PLoS One. 2011. PMID: 21949690 Free PMC article.
- Berries as a Treatment for Obesity-Induced Inflammation: Evidence from Preclinical Models.Land Lail H, Feresin RG, Hicks D, Stone B, Price E, Wanders D. Land Lail H, et al. Nutrients. 2021 Jan 23;13(2):334. doi: 10.3390/nu13020334. Nutrients. 2021. PMID: 33498671 Free PMC article. Review.
- Association between Consumption of Dietary Supplements and Chronic Kidney Disease Prevalence: Results of the Korean Nationwide Population-Based Survey.Fang Y, Lee H, Son S, Oh S, Jo SK, Cho W, Kim MG. Fang Y, et al. Nutrients. 2023 Feb 5;15(4):822. doi: 10.3390/nu15040822. Nutrients. 2023. PMID: 36839180 Free PMC article.
- Blueberry Consumption and Changes in Obesity and Diabetes Mellitus Outcomes: A Systematic Review.de Oliveira MS, Pellenz FM, de Souza BM, Crispim D. de Oliveira MS, et al. Metabolites. 2022 Dec 22;13(1):19. doi: 10.3390/metabo13010019. Metabolites. 2022. PMID: 36676944 Free PMC article. Review.
- Activation of angiotensin-converting enzyme 2 ameliorates metabolic syndrome-induced renal damage in rats by renal TLR4 and nuclear transcription factor κB downregulation.El-Domiaty HF, Sweed E, Kora MA, Zaki NG, Khodir SA. El-Domiaty HF, et al. Front Med (Lausanne). 2022 Aug 12;9:904756. doi: 10.3389/fmed.2022.904756. eCollection 2022. Front Med (Lausanne). 2022. PMID: 36035416 Free PMC article.
- Blueberry Supplementation in Midlife for Dementia Risk Reduction.Krikorian R, Skelton MR, Summer SS, Shidler MD, Sullivan PG. Krikorian R, et al. Nutrients. 2022 Apr 13;14(8):1619. doi: 10.3390/nu14081619. Nutrients. 2022. PMID: 35458181 Free PMC article. Clinical Trial.
- Blueberry as an Attractive Functional Fruit to Prevent (Pre)Diabetes Progression.Nunes S, Vieira P, Gomes P, Viana SD, Reis F. Nunes S, et al. Antioxidants (Basel). 2021 Jul 22;10(8):1162. doi: 10.3390/antiox10081162. Antioxidants (Basel). 2021. PMID: 34439410 Free PMC article. Review.
-
- Ervin RB (2009) Prevalence of metabolic syndrome among adults 20 years of age and over, by sex, age, race and ethnicity, and body mass index: United States, 2003–2006. Natl Health Stat Report: 1–7. - PubMed
-
- Elks CM, Francis J, Stull AJ, Cefalu WT, Shukitt-Hale B, et al... (2013) Overview of the Health Properties of Blueberries. In: Hunter MSaD, editor. Bioactives in Fruit: Health Benefits and Functional Foods Oxford, UK: John Wiley & Sons, Ltd. doi:10.1002/9781118635551.ch11.
- Animals
- Blueberry Plants / chemistry*
- Body Weight
- Diet*
- Disease Models, Animal
- Extracellular Signal-Regulated MAP Kinases / metabolism
- Gene Expression
- Glucose / metabolism
- Hemodynamics
- Kidney / metabolism*
- Kidney / pathology
- Kidney / physiopathology
- Kidney Function Tests
- Kidney Glomerulus / metabolism
- Kidney Glomerulus / pathology
- Male
- Metabolic Syndrome / genetics
- Metabolic Syndrome / metabolism*
- Metabolic Syndrome / physiopathology
- Mice, Knockout
- Mitogen-Activated Protein Kinases / metabolism
- NF-kappa B / metabolism
- Oxidation-Reduction
- Oxidative Stress*
- Phosphorylation
- Rats
- Toll-Like Receptor 4 / genetics
- Toll-Like Receptor 4 / metabolism
- p38 Mitogen-Activated Protein Kinases
- NF-kappa B
- Toll-Like Receptor 4
- Extracellular Signal-Regulated MAP Kinases
- Mitogen-Activated Protein Kinases
- p38 Mitogen-Activated Protein Kinases
- Glucose
- Full Text Sources
- Other Literature Sources
- Medical
- Miscellaneous
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
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![Figure 7. Effect of BB on MAPK…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4221362/bin/pone.0111976.g007.jpg)
Figure 8. Effect of BB on the…
Figure 8. Effect of BB on the renal inflammatory profile in MetS animals.
The (A)…
Figure 9. Effects of BB on antioxidant…
Figure 9. Effects of BB on antioxidant enzymes and Nrf2-Keap1 signaling in MetS animals.
Renal…
- Wild blueberry (Vaccinium angustifolium) consumption improves inflammatory status in the obese Zucker rat model of the metabolic syndrome.Vendrame S, Daugherty A, Kristo AS, Riso P, Klimis-Zacas D. Vendrame S, et al. J Nutr Biochem. 2013 Aug;24(8):1508-12. doi: 10.1016/j.jnutbio.2012.12.010. Epub 2013 Mar 1. J Nutr Biochem. 2013. PMID: 23465589
- Diet-induced renal changes in Zucker rats are ameliorated by the superoxide dismutase mimetic TEMPOL.Ebenezer PJ, Mariappan N, Elks CM, Haque M, Francis J. Ebenezer PJ, et al. Obesity (Silver Spring). 2009 Nov;17(11):1994-2002. doi: 10.1038/oby.2009.137. Epub 2009 May 7. Obesity (Silver Spring). 2009. PMID: 19424163 Free PMC article.
- Nitric oxide activates PI3-K and MAPK signalling pathways in human and rat vascular smooth muscle cells: influence of insulin resistance and oxidative stress.Doronzo G, Viretto M, Russo I, Mattiello L, Di Martino L, Cavalot F, Anfossi G, Trovati M. Doronzo G, et al. Atherosclerosis. 2011 May;216(1):44-53. doi: 10.1016/j.atherosclerosis.2011.01.019. Epub 2011 Jan 21. Atherosclerosis. 2011. PMID: 21316056
- A blueberry-enriched diet attenuates nephropathy in a rat model of hypertension via reduction in oxidative stress.Elks CM, Reed SD, Mariappan N, Shukitt-Hale B, Joseph JA, Ingram DK, Francis J. Elks CM, et al. PLoS One. 2011;6(9):e24028. doi: 10.1371/journal.pone.0024028. Epub 2011 Sep 15. PLoS One. 2011. PMID: 21949690 Free PMC article.
- Berries as a Treatment for Obesity-Induced Inflammation: Evidence from Preclinical Models.Land Lail H, Feresin RG, Hicks D, Stone B, Price E, Wanders D. Land Lail H, et al. Nutrients. 2021 Jan 23;13(2):334. doi: 10.3390/nu13020334. Nutrients. 2021. PMID: 33498671 Free PMC article. Review.
- Association between Consumption of Dietary Supplements and Chronic Kidney Disease Prevalence: Results of the Korean Nationwide Population-Based Survey.Fang Y, Lee H, Son S, Oh S, Jo SK, Cho W, Kim MG. Fang Y, et al. Nutrients. 2023 Feb 5;15(4):822. doi: 10.3390/nu15040822. Nutrients. 2023. PMID: 36839180 Free PMC article.
- Blueberry Consumption and Changes in Obesity and Diabetes Mellitus Outcomes: A Systematic Review.de Oliveira MS, Pellenz FM, de Souza BM, Crispim D. de Oliveira MS, et al. Metabolites. 2022 Dec 22;13(1):19. doi: 10.3390/metabo13010019. Metabolites. 2022. PMID: 36676944 Free PMC article. Review.
- Activation of angiotensin-converting enzyme 2 ameliorates metabolic syndrome-induced renal damage in rats by renal TLR4 and nuclear transcription factor κB downregulation.El-Domiaty HF, Sweed E, Kora MA, Zaki NG, Khodir SA. El-Domiaty HF, et al. Front Med (Lausanne). 2022 Aug 12;9:904756. doi: 10.3389/fmed.2022.904756. eCollection 2022. Front Med (Lausanne). 2022. PMID: 36035416 Free PMC article.
- Blueberry Supplementation in Midlife for Dementia Risk Reduction.Krikorian R, Skelton MR, Summer SS, Shidler MD, Sullivan PG. Krikorian R, et al. Nutrients. 2022 Apr 13;14(8):1619. doi: 10.3390/nu14081619. Nutrients. 2022. PMID: 35458181 Free PMC article. Clinical Trial.
- Blueberry as an Attractive Functional Fruit to Prevent (Pre)Diabetes Progression.Nunes S, Vieira P, Gomes P, Viana SD, Reis F. Nunes S, et al. Antioxidants (Basel). 2021 Jul 22;10(8):1162. doi: 10.3390/antiox10081162. Antioxidants (Basel). 2021. PMID: 34439410 Free PMC article. Review.
-
- Ervin RB (2009) Prevalence of metabolic syndrome among adults 20 years of age and over, by sex, age, race and ethnicity, and body mass index: United States, 2003–2006. Natl Health Stat Report: 1–7. - PubMed
-
- Elks CM, Francis J, Stull AJ, Cefalu WT, Shukitt-Hale B, et al... (2013) Overview of the Health Properties of Blueberries. In: Hunter MSaD, editor. Bioactives in Fruit: Health Benefits and Functional Foods Oxford, UK: John Wiley & Sons, Ltd. doi:10.1002/9781118635551.ch11.
- Animals
- Blueberry Plants / chemistry*
- Body Weight
- Diet*
- Disease Models, Animal
- Extracellular Signal-Regulated MAP Kinases / metabolism
- Gene Expression
- Glucose / metabolism
- Hemodynamics
- Kidney / metabolism*
- Kidney / pathology
- Kidney / physiopathology
- Kidney Function Tests
- Kidney Glomerulus / metabolism
- Kidney Glomerulus / pathology
- Male
- Metabolic Syndrome / genetics
- Metabolic Syndrome / metabolism*
- Metabolic Syndrome / physiopathology
- Mice, Knockout
- Mitogen-Activated Protein Kinases / metabolism
- NF-kappa B / metabolism
- Oxidation-Reduction
- Oxidative Stress*
- Phosphorylation
- Rats
- Toll-Like Receptor 4 / genetics
- Toll-Like Receptor 4 / metabolism
- p38 Mitogen-Activated Protein Kinases
- NF-kappa B
- Toll-Like Receptor 4
- Extracellular Signal-Regulated MAP Kinases
- Mitogen-Activated Protein Kinases
- p38 Mitogen-Activated Protein Kinases
- Glucose
- Full Text Sources
- Other Literature Sources
- Medical
- Miscellaneous
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Figure 8. Effect of BB on the…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4221362/bin/pone.0111976.g008.jpg)
Figure 9. Effects of BB on antioxidant…
Figure 9. Effects of BB on antioxidant enzymes and Nrf2-Keap1 signaling in MetS animals.
Renal…
- Wild blueberry (Vaccinium angustifolium) consumption improves inflammatory status in the obese Zucker rat model of the metabolic syndrome.Vendrame S, Daugherty A, Kristo AS, Riso P, Klimis-Zacas D. Vendrame S, et al. J Nutr Biochem. 2013 Aug;24(8):1508-12. doi: 10.1016/j.jnutbio.2012.12.010. Epub 2013 Mar 1. J Nutr Biochem. 2013. PMID: 23465589
- Diet-induced renal changes in Zucker rats are ameliorated by the superoxide dismutase mimetic TEMPOL.Ebenezer PJ, Mariappan N, Elks CM, Haque M, Francis J. Ebenezer PJ, et al. Obesity (Silver Spring). 2009 Nov;17(11):1994-2002. doi: 10.1038/oby.2009.137. Epub 2009 May 7. Obesity (Silver Spring). 2009. PMID: 19424163 Free PMC article.
- Nitric oxide activates PI3-K and MAPK signalling pathways in human and rat vascular smooth muscle cells: influence of insulin resistance and oxidative stress.Doronzo G, Viretto M, Russo I, Mattiello L, Di Martino L, Cavalot F, Anfossi G, Trovati M. Doronzo G, et al. Atherosclerosis. 2011 May;216(1):44-53. doi: 10.1016/j.atherosclerosis.2011.01.019. Epub 2011 Jan 21. Atherosclerosis. 2011. PMID: 21316056
- A blueberry-enriched diet attenuates nephropathy in a rat model of hypertension via reduction in oxidative stress.Elks CM, Reed SD, Mariappan N, Shukitt-Hale B, Joseph JA, Ingram DK, Francis J. Elks CM, et al. PLoS One. 2011;6(9):e24028. doi: 10.1371/journal.pone.0024028. Epub 2011 Sep 15. PLoS One. 2011. PMID: 21949690 Free PMC article.
- Berries as a Treatment for Obesity-Induced Inflammation: Evidence from Preclinical Models.Land Lail H, Feresin RG, Hicks D, Stone B, Price E, Wanders D. Land Lail H, et al. Nutrients. 2021 Jan 23;13(2):334. doi: 10.3390/nu13020334. Nutrients. 2021. PMID: 33498671 Free PMC article. Review.
- Association between Consumption of Dietary Supplements and Chronic Kidney Disease Prevalence: Results of the Korean Nationwide Population-Based Survey.Fang Y, Lee H, Son S, Oh S, Jo SK, Cho W, Kim MG. Fang Y, et al. Nutrients. 2023 Feb 5;15(4):822. doi: 10.3390/nu15040822. Nutrients. 2023. PMID: 36839180 Free PMC article.
- Blueberry Consumption and Changes in Obesity and Diabetes Mellitus Outcomes: A Systematic Review.de Oliveira MS, Pellenz FM, de Souza BM, Crispim D. de Oliveira MS, et al. Metabolites. 2022 Dec 22;13(1):19. doi: 10.3390/metabo13010019. Metabolites. 2022. PMID: 36676944 Free PMC article. Review.
- Activation of angiotensin-converting enzyme 2 ameliorates metabolic syndrome-induced renal damage in rats by renal TLR4 and nuclear transcription factor κB downregulation.El-Domiaty HF, Sweed E, Kora MA, Zaki NG, Khodir SA. El-Domiaty HF, et al. Front Med (Lausanne). 2022 Aug 12;9:904756. doi: 10.3389/fmed.2022.904756. eCollection 2022. Front Med (Lausanne). 2022. PMID: 36035416 Free PMC article.
- Blueberry Supplementation in Midlife for Dementia Risk Reduction.Krikorian R, Skelton MR, Summer SS, Shidler MD, Sullivan PG. Krikorian R, et al. Nutrients. 2022 Apr 13;14(8):1619. doi: 10.3390/nu14081619. Nutrients. 2022. PMID: 35458181 Free PMC article. Clinical Trial.
- Blueberry as an Attractive Functional Fruit to Prevent (Pre)Diabetes Progression.Nunes S, Vieira P, Gomes P, Viana SD, Reis F. Nunes S, et al. Antioxidants (Basel). 2021 Jul 22;10(8):1162. doi: 10.3390/antiox10081162. Antioxidants (Basel). 2021. PMID: 34439410 Free PMC article. Review.
-
- Ervin RB (2009) Prevalence of metabolic syndrome among adults 20 years of age and over, by sex, age, race and ethnicity, and body mass index: United States, 2003–2006. Natl Health Stat Report: 1–7. - PubMed
-
- Elks CM, Francis J, Stull AJ, Cefalu WT, Shukitt-Hale B, et al... (2013) Overview of the Health Properties of Blueberries. In: Hunter MSaD, editor. Bioactives in Fruit: Health Benefits and Functional Foods Oxford, UK: John Wiley & Sons, Ltd. doi:10.1002/9781118635551.ch11.
- Animals
- Blueberry Plants / chemistry*
- Body Weight
- Diet*
- Disease Models, Animal
- Extracellular Signal-Regulated MAP Kinases / metabolism
- Gene Expression
- Glucose / metabolism
- Hemodynamics
- Kidney / metabolism*
- Kidney / pathology
- Kidney / physiopathology
- Kidney Function Tests
- Kidney Glomerulus / metabolism
- Kidney Glomerulus / pathology
- Male
- Metabolic Syndrome / genetics
- Metabolic Syndrome / metabolism*
- Metabolic Syndrome / physiopathology
- Mice, Knockout
- Mitogen-Activated Protein Kinases / metabolism
- NF-kappa B / metabolism
- Oxidation-Reduction
- Oxidative Stress*
- Phosphorylation
- Rats
- Toll-Like Receptor 4 / genetics
- Toll-Like Receptor 4 / metabolism
- p38 Mitogen-Activated Protein Kinases
- NF-kappa B
- Toll-Like Receptor 4
- Extracellular Signal-Regulated MAP Kinases
- Mitogen-Activated Protein Kinases
- p38 Mitogen-Activated Protein Kinases
- Glucose
- Full Text Sources
- Other Literature Sources
- Medical
- Miscellaneous
![Figure 9. Effects of BB on antioxidant…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4221362/bin/pone.0111976.g009.jpg)
References
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Source: PubMed