ArticleJournal of lipid research2014
Upregulation of hepatic VLDLR via PPARα is required for the triglyceride-lowering effect of fenofibrate.
Article in Journal of lipid research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 59 citations in OpenAlex.
- Longevity-driven hepatic transcriptional programs mediate resilience to diet-induced liver injury in Ames dwarf mice.GeroScience · 2026Article
- Dyslipidaemia and hepatic steatosis: mechanisms and implications for lipid-lowering therapy.Nature reviews. Cardiology · 2026Review
- VLDLR: A Multifunctional receptor in diverse pathophysiological processes.Cell communication and signaling : CCS · 2026Review
- Systems-Level Integration of Multi-Omics Identifies Genetic Modifiers of TANGO2 Deficiency Disorder.Biomolecules · 2025Article
- Zebrafish model of palmitic acid induced MAFLD recapitulates pathways conserved in mice and humans.Scientific reports · 2025Article
- Sex-specific metabolic responses to high-fat diet in mice with NOX4 deficiency.Redox biology · 2025Article
- Fenofibrate Treatment Inhibits Very-Low-Density Lipoprotein Transport Vesicle Formation by Reducing Sar1b Protein Expression.International journal of molecular sciences · 2025Article
- Dose-Dependent PFESA-BP2 Exposure Increases Risk of Liver Toxicity and Hepatocellular Carcinoma.Current issues in molecular biology · 2025Article
- A sexually dimorphic hepatic cycle of periportal VLDL generation and subsequent pericentral VLDLR-mediated re-uptake.Nature communications · 2024Article
- SIRT1 regulates hepatic vldlr levels.Cell communication and signaling : CCS · 2024Article
- Short-Term Growth Hormone Administration Mediates Hepatic Fatty Acid Uptake and De Novo Lipogenesis Gene Expression in Obese Rats.Biomedicines · 2023Article
- Microarray analysis identifies coding and non-coding RNA markers of liver injury in whole body irradiated mice.Scientific reports · 2023Article
- Emerging Evidence of Pathological Roles of Very-Low-Density Lipoprotein (VLDL).International journal of molecular sciences · 2022Review
- Peroxisome Proliferator-Activated Receptor Activation in Precision-Cut Bovine Liver Slices Reveals Novel Putative PPAR Targets in Periparturient Dairy Cows.Frontiers in veterinary science · 2022Article
- Epigenetic State Changes Underlie Metabolic Switch in Mouse Post-Infarction Border Zone Cardiomyocytes.Journal of cardiovascular development and disease · 2021Article
- Very low-density lipoprotein receptor increases in a liver-specific manner due to protein deficiency but does not affect fatty liver in mice.Scientific reports · 2021Article
- Transcriptional Regulation of Metabolic Pathways via Lipid-Sensing Nuclear Receptors PPARs, FXR, and LXR in NASH.Cellular and molecular gastroenterology and hepatology · 2021Review
- Target Deconvolution of Fenofibrate in Nonalcoholic Fatty Liver Disease Using Bioinformatics Analysis.BioMed research international · 2021Article
- Trace Elements, PPARs, and Metabolic Syndrome.International journal of molecular sciences · 2020Review
- Pemafibrate, a New Selective PPARα Modulator: Drug Concept and Its Clinical Applications for Dyslipidemia and Metabolic Diseases.Current atherosclerosis reports · 2020Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The liver and the VLDL receptor (VLDLR) play major roles in TG and VLDL metabolism. However, the exact role of liver VLDLR is not well known because of the absence of or difficulty in detecting VLDLR in the liver. In this study, we demonstrate that fenofibrate, a PPARα agonist and widely used TG-lowering drug, markedly upregulated hepatic VLDLR, which is essential for lowering TG. This study also shows that the distinct regulatory roles of PPARα agonists on VLDLR in the liver and peripheral tissues including adipose tissues, heart, and skeletal muscles are due to the pattern of expression of PPARα. The in vivo portion of our study demonstrated that oral fenofibrate robustly increased liver VLDLR expression levels in hyperlipidemic and diabetic mice and significantly reduced the increase in serum TG observed in wt mice after feeding with high-fat diet (HFD) but not in Vldlr(-/-) mice or Pparα(-/-) mice. However, overexpression of mouse VLDLR in livers of Vldlr(-/-) mice significantly prevented the increase in serum TG induced by HFD. The in vitro portion of our study showed that fenofibrate upregulated VLDLR transcriptional activity through PPAR response element binding to the VLDLR promoter. The conclusions of our study provide a novel mechanism for the TG-lowering effects of fenofibrate in the treatment of dyslipidemia.
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