The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
PPARα agonist fenofibrate enhances fatty acid β-oxidation and attenuates polycystic kidney and liver disease in mice
Open accessAbstract
Peroxisome proliferator-activated receptor α (PPARα) is a nuclear hormone receptor that promotes fatty acid β-oxidation (FAO) and oxidative phosphorylation (OXPHOS). We and others have recently shown that PPARα and its target genes are downregulated, and FAO and OXPHOS are impaired in autosomal dominant polycystic kidney disease (ADPKD). However, whether PPARα and FAO/OXPHOS are causally linked to ADPKD progression is not entirely clear. We report that expression of PPARα and FAO/OXPHOS genes is downregulated, and in vivo β-oxidation rate of 3 H-labeled triolein is reduced in Pkd1 RC/RC mice, a slowly progressing orthologous model of ADPKD that closely mimics the human ADPKD phenotype. To evaluate the effects of upregulating PPARα, we conducted a 5-mo, randomized, preclinical trial by treating Pkd1 RC/RC mice with fenofibrate, a clinically available PPARα agonist. Fenofibrate treatment resulted in increased expression of PPARα and FAO/OXPHOS genes, upregulation of peroxisomal and mitochondrial biogenesis markers, and higher β-oxidation rates in Pkd1 RC/RC kidneys. MRI-assessed total kidney volume and total cyst volume, kidney-weight-to-body-weight ratio, cyst index, and serum creatinine levels were significantly reduced in fenofibrate-treated compared with untreated littermate Pkd1 RC/RC mice. Moreover, fenofibrate treatment was associated with reduced kidney cyst proliferation and infiltration by inflammatory cells, including M2-like macrophages. Finally, fenofibrate treatment also reduced bile duct cyst number, cyst proliferation, and liver inflammation and fibrosis. In conclusion, our studies suggest that promoting PPARα activity to enhance mitochondrial metabolism may be a useful therapeutic strategy for ADPKD.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Conversely, improved mitochondrial function -including enhanced oxidative phosphorylation and mitochondrial biogenesis- has been consistently associated with macrophage reprogramming and fibrosis resolution (28–31).”
From Strategies to promote liver fibrosis amelioration with involvement of restorative macrophages (2026) · cites this paper as [30]
In the citing paper
“Pharmacological activation of PPARα increases restorative macrophage populations (30), and its upregulation, together with PPARγ, may depend on AMPK activation, linking transcriptional control with metabolic reprogramming (35).”
From Strategies to promote liver fibrosis amelioration with involvement of restorative macrophages (2026) · cites this paper as [30]
Citations
Cites
Cancer cell metabolism: warburg and beyond
Hsu, P. P., & Sabatini, D. M. (2008) · Cell · doi:10.1016/j.cell.2008.08.021 · Cited by 2,452 · cited 1×
“To meet these needs, cyst epithelial cells appear to rewire their metabolism by activating alternative pathways of glycolysis and glutaminolysis (11, 27).”
BackgroundMechanism of Action of Fibrates on Lipid and Lipoprotein Metabolism
Staels, B., Dallongeville, J., Auwerx, J., Schoonjans, K., Leitersdorf, E., & Fruchart, J.-C. (1998) · Circulation · doi:10.1161/01.cir.98.19.2088 · Cited by 1,786
Tolvaptan in Patients with Autosomal Dominant Polycystic Kidney Disease
Torres, V. E., Chapman, A. B., Devuyst, O., Gansevoort, R. T., Grantham, J. J., Higashihara, E., Perrone, R. D., Krasa, H. B., Ouyang, J., & Czerwiec, F. S. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1205511 · Cited by 1,657
Kang, H. M., Ahn, S. H., Choi, P., Ko, Y.-A., Han, S. H., Chinga, F., Park, A. S. D., Tao, J., Sharma, K., Pullman, J., et al. (2015) · Nature Medicine · doi:10.1038/nm.3762 · Cited by 1,555
MicroRNA-21 Promotes Fibrosis of the Kidney by Silencing Metabolic Pathways
Chau, B. N., Xin, C., Hartner, J. C., Ren, S., Castaño, A. P., Linn, G. R., Li, J., Tran, P. T., Kaimal, V., Huang, X., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003205 · Cited by 611
PGC1α drives NAD biosynthesis linking oxidative metabolism to renal protection
Tran, M. T., Zsengellér, Z. K., Berg, A. H., Khankin, E. V., Bhasin, M., Kim, W., Clish, C. B., Stillman, I. E., Karumanchi, S. A., Rhee, E. P., et al. (2016) · Nature · doi:10.1038/nature17184 · Cited by 546
Defective glucose metabolism in polycystic kidney disease identifies a new therapeutic strategy
Rowe, I., Chiaravalli, M., Mannella, V., Ulisse, V., Quilici, G., Pema, M., Song, X. W., Xu, H., Mari, S., Qian, F., et al. (2013) · Nature Medicine · doi:10.1038/nm.3092 · Cited by 503
Kusminski, C. M., Holland, W. L., Sun, K., Park, J., Spurgin, S. B., Lin, Y., Askew, G. R., Simcox, J., McClain, D. A., Li, C., et al. (2012) · Nature Medicine · doi:10.1038/nm.2899 · Cited by 474
Self-citationFunctional polycystin-1 dosage governs autosomal dominant polycystic kidney disease severity
Hopp, K., Ward, C. J., Hommerding, C. J., Nasr, S. H., Tuan, H.-F., Gainullin, V. G., Rossetti, S., Torres, V. E., & Harris, P. C. (2012) · Journal of Clinical Investigation · doi:10.1172/jci64313 · Cited by 442
Bae, K. T., Zhu, F., Chapman, A. B., Torres, V. E., Grantham, J. J., Guay‐Woodford, L. M., Baumgarten, D. A., King, B. F., Wetzel, L. H., Kenney, P. J., et al. (2005) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.00080605 · Cited by 311
Cited by
Sorted by citations
Kidney lipid dysmetabolism and lipid droplet accumulation in chronic kidney disease
Mitrofanova, A. V., Merscher, S., & Fornoni, A. (2023) · Nature Reviews Nephrology · doi:10.1038/s41581-023-00741-w · Cited by 382
Ketosis Ameliorates Renal Cyst Growth in Polycystic Kidney Disease
Torres, J. A., Kruger, S. L., Broderick, C., Amarlkhagva, T., Agrawal, S., Dodam, J. R., Mrug, M. M., Lyons, L. A., & Weimbs, T. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.09.012 · Cited by 223
Lee, E. C. Y., Valencia, T., Allerson, C. R., Schairer, A., Flaten, A., Yheskel, M., Kersjes, K., Li, J., Gatto, S., Takhar, M. M., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11918-y · Cited by 193
Self-citationMetabolism and mitochondria in polycystic kidney disease research and therapy
Padovano, V., Podrini, C., Boletta, A., & Caplan, M. J. (2018) · Nature Reviews Nephrology · doi:10.1038/s41581-018-0051-1 · Cited by 182
Defective Mitochondrial Fatty Acid Oxidation and Lipotoxicity in Kidney Diseases
Jang, H., Noh, M. R., Kim, J., & Padanilam, B. J. (2020) · Frontiers in Medicine · doi:10.3389/fmed.2020.00065 · Cited by 170
Metadata
- Authors
- Lakhia, R., Yheskel, M., Flaten, A., Quittner-Strom, E. B., Holland, W. L., & Patel, V.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Patel, Vishal
- ORCID
- Venue
- American Journal of Physiology-Renal Physiology
- Publisher
- American Physiological Society
- Published
- 2018-01-01
- Volume
- 314
- Issue
- 1
- Pages
- F122-F131
- ISSN
- 1522-1466 (ISSN-L)
- 1931-857X
- PMC
- PMC5866355
- OpenAlex
- W2754464449
- Cited by
- 140
- References
- 38
- Citations by year
- 2026: 19 · 2025: 19 · 2024: 21 · 2023: 15 · 2022: 20 · 2021: 15 · 2020: 17 · 2019: 11 · 2018: 3
- FWCI
- 5.63
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- American Journal of Physiology-Renal Physiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (DK102572)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Genetics (clinical) › Tuberous Sclerosis Complex Research
- Keywords
- PPARα, fenofibrate, fatty acid beta-oxidation, oxidative phosphorylation, autosomal dominant polycystic kidney disease, mitochondrial biogenesis, peroxisome biogenesis, renal cysts, bile duct cyst, liver fibrosis, M2 macrophages, liver inflammation, mitochondrial metabolism
- MeSH terms
- Animals, Cysts, Fatty Acids, Fatty Liver, Polycystic Kidney Diseases, Liver Diseases, Mice, Transgenic, Oxidation-Reduction, Transcription Factors, PPAR alpha
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
