PPARα agonist fenofibrate improves diabetic nephropathy in db/db mice
Open accessAbstract
Peroxisome proliferator-activated receptor alpha (PPARalpha) is a member of the ligand-activated nuclear receptor superfamily, and plays an important role in lipid metabolism and glucose homeostasis. The purpose of this study is to determine whether the activation of PPARalpha by fenofbrate would improve diabetes and its renal complications in type II diabetes mellitus. Male C57 BLKS db/db mice and db/m controls at 8 weeks of age were divided to receive either a regular diet chow (db/db, n=8; db/m, n=6) or a diet containing fenofibrate (db/db, n=8; db/m, n=7). Mice were followed for 8 weeks. Fenofibrate treatment dramatically reduced fasting blood glucose (P<0.001) and HbA1c levels (P<0.001), and was associated with decreased food intake (P<0.01) and slightly reduced body weight. Fenofibrate also ameliorated insulin resistance (P<0.001) and reduced plasma insulin levels (P<0.05) in db/db mice. Hypertrophy of pancreatic islets was decreased and insulin content markedly increased (P<0.05) in fenofibrate-treated diabetic animals. In addition, fenofibrate treatment significantly reduced urinary albumin excretion (P<0.001). This was accompanied by dramatically reduced glomerular hypertrophy and mesangial matrix expansion. Furthermore, the addition of fenofibrate to cultured mesangial cells, which possess functional active PPARalpha, decreased type I collagen production. Taken together, the PPARalpha agonist fenofibrate dramatically improves hyperglycemia, insulin resistance, albuminuria, and glomerular lesions in db/db mice. The activation of PPARalpha by fenofibrate in mesangial cells may partially contribute to its renal protection. Thus, fenofibrate may serve as a therapeutic agent for type II diabetes and diabetic nephropathy.
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Fenofibrate has been shown to decrease albuminuria in a mouse model of type 2 diabetes and in humans.
“Fenofibrate has been shown to decrease albuminuria in a mouse model of type 2 diabetes [10] and in humans [1,2,11].”
Fenofibrate use in a mouse model of type 2 diabetes was linked with reduction in albuminuria, as well as histopathological improvements, e.g. reduced glomerular hypertrophy and reduced mesangial expansion.
“Interestingly, fenofibrate use in a mouse model of type 2 diabetes was linked with reduction in albuminuria, as well as histopathological improvements, e.g.reduced glomerular hypertrophy and reduced mesangial expansion [10].”
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- Authors
- Park, C. W., Zhang, Y., Zhang, X., Wu, J., Chen, L., Cha, D. R., Su, D., Hwang, M.-T., Fan, X., Davis, L., Striker, G., Zheng, F., Breyer, M., & Guan, Y.
- Affiliations
- Vanderbilt University Medical Center (US)
- Peking University (CN)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Guan, Y.
- Venue
- Kidney International
- Publisher
- Elsevier BV
- Published
- 2006-05
- Volume
- 69
- Issue
- 9
- Pages
- 1511-1517
- ISSN
- 0085-2538 (ISSN-L)
- OpenAlex
- W2042646534
- Cited by
- 202
- References
- 2
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 9 · 2023: 7 · 2022: 7 · 2021: 10 · 2020: 10 · 2019: 8 · 2018: 11 · 2017: 9 · 2016: 9 · 2015: 10 · 2014: 9 · 2013: 10 · 2012: 13
- FWCI
- 5.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Kidney International (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China
- National Institutes of Health (5r01dk065074-05)
- National Institute of Diabetes and Digestive and Kidney Diseases (R21DK064118, DK065074-02, P01-DK 38226, DK 38226, P01DK038226, DK64118)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Keywords
- fenofibrate, PPARα agonist, diabetic nephropathy, type 2 diabetes, db/db mice, insulin resistance, albuminuria, glomerular hypertrophy, mesangial expansion, mesangial cells, type I collagen, renal protection
- MeSH terms
- Albuminuria, Animals, Hypolipidemic Agents, Blood Glucose, Body Weight, Cells, Cultured, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Glycated Hemoglobin, Hyperglycemia, Insulin, Insulin Resistance, Islets of Langerhans, Kidney Glomerulus, Male, Mice, Mutant Strains, Fenofibrate, Treatment Outcome, Collagen Type I, PPAR alpha, Mesangial Cells, Mice
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