ArticleBMC genomics2018
The whole transcriptome effects of the PPARα agonist fenofibrate on livers of hepatocyte humanized mice.
Article in BMC genomics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 47 citations in OpenAlex.
- Effects of fenofibrate on angiopoietin-like 3/4/8 proteins and apolipoprotein A5.Journal of lipid research · 2026Article
- Integration of mechanistic and repeat dose toxicity data in the derivation of an oral reference dose for HFPO-DA.Toxicological sciences : an official journal of the Society of Toxicology · 2026Review
- A systems-level integration of liver-kidney transcriptomics and genome-scale metabolic models reveals organ-specific injury mechanisms.Frontiers in toxicology · 2026Article
- Fenofibrate differentially activates PPARα-mediated lipid metabolism in rat kidney and liver.Scientific reports · 2025Article
- Lipid metabolism orchestrates liver regeneration: an integrated metabolic network.Journal of translational medicine · 2025Review
- Assessing the impact of perfluoroalkyl substances on liver health: a comprehensive study using multi-donor human liver spheroids.Environment international · 2025Article
- Exposure to low-dose perfluorooctanoic acid promotes hepatic steatosis and disrupts the hepatic transcriptome in mice.Molecular metabolism · 2022Article
- Capparis spinosa improves non-alcoholic steatohepatitis through down-regulating SREBP-1c and a PPARα-independent pathway in high-fat diet-fed rats.BMC research notes · 2022Article
- Transcriptomic Analysis Revealed an Important Role of Peroxisome-Proliferator-Activated Receptor Alpha Signaling in Src Homology Region 2 Domain-Containing Phosphatase-1 Insufficiency Leading to the Development of Renal Ischemia-Reperfusion Injury.Frontiers in medicine · 2022Article
- Estimating Drug Efficacy with a Diet-Induced NASH Model in Chimeric Mice with Humanized Livers.Biomedicines · 2021Article
- Application of humanized mice to toxicology studies: Evaluation of the human relevance of the mode of action for rodent liver tumor formation by activators of the constitutive androstane receptor (CAR).Journal of toxicologic pathology · 2021Article
- Hepatic lipid droplets: A balancing act between energy storage and metabolic dysfunction in NAFLD.Molecular metabolism · 2021Review
- Beneficial effects of elafibranor on NASH in E3L.CETP mice and differences between mice and men.Scientific reports · 2021Article
- Nonalcoholic steatohepatitis: the role of peroxisome proliferator-activated receptors.Nature reviews. Gastroenterology & hepatology · 2021Review
- Transcriptomic analyses of livers from mice exposed to 1,4-dioxane for up to 90 days to assess potential mode(s) of action underlying liver tumor development.Current research in toxicology · 2021Article
- Protein acetylation in mitochondria plays critical functions in the pathogenesis of fatty liver disease.BMC genomics · 2020Article
- Fat-lowering effects of isorhamnetin are via NHR-49-dependent pathway inCurrent research in food science · 2020Article
- The pharmacodynamic and differential gene expression analysis of PPAR α/δ agonist GFT505 in CDAHFD-induced NASH model.PloS one · 2020Article
- Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundThe role of PPARα in gene regulation in mouse liver is well characterized. However, less is known about the role of PPARα in human liver. The aim of the present study was to better characterize the impact of PPARα activation on gene regulation in human liver. To that end, chimeric mice containing hepatocyte humanized livers were given an oral dose of 300 mg/kg fenofibrate daily for 4 days. Livers were collected and analyzed by hematoxilin and eosin staining, qPCR, and transcriptomics. Transcriptomics data were compared with existing datasets on PPARα activation in normal mouse liver, human primary hepatocytes, and human precision cut liver slices.
resultsOf the different human liver models, the gene expression profile of hepatocyte humanized livers most closely resembled actual human liver. In the hepatocyte humanized mouse livers, the human hepatocytes exhibited excessive lipid accumulation. Fenofibrate increased the size of the mouse but not human hepatocytes, and tended to reduce steatosis in the human hepatocytes. Quantitative PCR indicated that induction of PPARα targets by fenofibrate was less pronounced in the human hepatocytes than in the residual mouse hepatocytes. Transcriptomics analysis indicated that, after filtering, a total of 282 genes was significantly different between fenofibrate- and control-treated mice (P < 0.01). 123 genes were significantly lower and 159 genes significantly higher in the fenofibrate-treated mice, including many established PPARα targets such as FABP1, HADHB, HADHA, VNN1, PLIN2, ACADVL and HMGCS2. According to gene set enrichment analysis, fenofibrate upregulated interferon/cytokine signaling-related pathways in hepatocyte humanized liver, but downregulated these pathways in normal mouse liver. Also, fenofibrate downregulated pathways related to DNA synthesis in hepatocyte humanized liver but not in normal mouse liver.
conclusionThe results support the major role of PPARα in regulating hepatic lipid metabolism, and underscore the more modest effect of PPARα activation on gene regulation in human liver compared to mouse liver. The data suggest that PPARα may have a suppressive effect on DNA synthesis in human liver, and a stimulatory effect on interferon/cytokine signalling.
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