Cited by 80Peroxisome Proliferator-Activated ReceptorsChronic Kidney Disease and DiabetesAutophagy in Disease and Therapy

Delayed treatment with fenofibrate protects against high-fat diet-induced kidney injury in mice: the possible role of AMPK autophagy

Sohn, Minji, Kim, Keumji, Uddin, Md Jamal, Lee, Gayoung, Hwang, Inah, Kang, Hyeji, Kim, Hyunji, Lee, Jung Hwa +1 more·2017·American Journal of Physiology-Renal Physiology

Abstract

Fenofibrate activates not only peroxisome proliferator-activated receptor-α (PPARα) but also adenosine monophosphate-activated protein kinase (AMPK). AMPK-mediated cellular responses protect kidney from high-fat diet (HFD)-induced injury, and autophagy resulting from AMPK activation has been regarded as a stress-response mechanism. Thus the present study examined the role of AMPK and autophagy in the renotherapeutic effects of fenofibrate. C57BL/6J mice were divided into three groups: normal diet (ND), HFD, and HFD + fenofibrate (HFD + FF). Fenofibrate was administered 4 wk after the initiation of the HFD when renal injury was initiated. Mouse proximal tubule cells (mProx24) were used to clarify the role of AMPK. Feeding mice with HFD for 12 wk induced insulin resistance and kidney injury such as albuminuria, glomerulosclerosis, tubular injury, and inflammation, which were effectively inhibited by fenofibrate. In addition, fenofibrate treatment resulted in the activation of renal AMPK, upregulation of fatty acid oxidation (FAO) enzymes and antioxidants, and induction of autophagy in the HFD mice. In mProx24 cells, fenofibrate activated AMPK in a concentration-dependent manner, upregulated FAO enzymes and antioxidants, and induced autophagy, all of which were inhibited by treatment of compound C, an AMPK inhibitor. Fenofibrate-induced autophagy was also significantly blocked by AMPKα1 siRNA but not by PPARα siRNA. Collectively, these results demonstrate that delayed treatment with fenofibrate has a therapeutic effect on HFD-induced kidney injury, at least in part, through the activation of AMPK and induction of subsequent downstream effectors: autophagy, FAO enzymes, and antioxidants.

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Crossref · 10.1152/ajprenal.00596.2015

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Authors
Sohn, M., Kim, K., Uddin, M. J., Lee, G., Hwang, I., Kang, H., Kim, H., Lee, J. H., & Ha, H.
Affiliations
  • Ewha Womans University (KR)
  • Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, Korea
Corresponding author
Ha, Hunjoo
Venue
American Journal of Physiology-Renal Physiology
Published
2017-02-01
Volume
312
Issue
2
Pages
F323-F334
ISSN
  • 1522-1466 (ISSN-L)
  • 1931-857X
OpenAlex
W2501972755
Cited by
80
References
48
Citations by year
2026: 6 · 2025: 7 · 2024: 9 · 2023: 11 · 2022: 15 · 2021: 8 · 2020: 10 · 2019: 5 · 2018: 4 · 2017: 5
FWCI
2.43
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Physiology-Renal Physiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Ministry of Education, Science and Technology (Korean Ministry of Education, Science and Technology) (2012R1A2A1A0300692 and 2016R1A2B4006575, 2015H1D3A1062189)
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 › Epidemiology › Autophagy in Disease and Therapy
Keywords
fenofibrate, AMPK, autophagy, high-fat diet, kidney injury, PPARα, fatty acid oxidation, antioxidants, albuminuria, glomerulosclerosis, proximal tubular epithelial cells, insulin resistance, renal protection, treatment delay
MeSH terms
Albuminuria, Animals, Hypolipidemic Agents, Autophagy, Diabetic Nephropathies, Dose-Response Relationship, Drug, Insulin Resistance, Kidney Tubules, Proximal, Phosphorylation, Fenofibrate, Signal Transduction, Protective Agents, Mice, AMP-Activated Protein Kinases, Diet, High-Fat

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