ArticleMolecular metabolism2018
Hepatic regulation of VLDL receptor by PPARβ/δ and FGF21 modulates non-alcoholic fatty liver disease.
Article in Molecular metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 110 citations in OpenAlex.
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- Hepatokines and polycystic ovary syndrome: investigating the connection between the hepato-ovarian axis and disorders in glycolipid metabolism in PCOS: a narrative review.Frontiers in endocrinology · 2026Review
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- Dimorphic regulation of time-restricted feeding effects by hepatocyte Period 1.Molecular metabolism · 2025Article
- Secreted proteins in treating metabolic dysfunction-associated steatotic liver disease: from bench towards bedside.Protein & cell · 2025Review
- Lipid Accumulation and Insulin Resistance: Bridging Metabolic Dysfunction-Associated Fatty Liver Disease and Chronic Kidney Disease.International journal of molecular sciences · 2025Review
- Metabolic Dysfunction-Associated Steatotic Liver Disease: From a Very Low-Density Lipoprotein Perspective.Biomolecules · 2025Review
- Orchestration of Gut-Liver-Associated Transcription Factors in MAFLD: From Cross-Organ Interactions to Therapeutic Innovation.Biomedicines · 2025Review
- White adipose tissue browning and peroxisome proliferator activated receptors in MASLD.Frontiers in endocrinology · 2025Review
- Targeting lipophagy and nuclear receptors in metabolic-associated fatty liver disease: insights from traditional Chinese medicine.Frontiers in pharmacology · 2025Review
- Novel intervention for alcohol-associated liver disease.World journal of gastroenterology · 2024Article
- A sexually dimorphic hepatic cycle of periportal VLDL generation and subsequent pericentral VLDLR-mediated re-uptake.Nature communications · 2024Article
- Tackling exosome and nuclear receptor interaction: an emerging paradigm in the treatment of chronic diseases.Military Medical Research · 2024Review
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- Targeting lipid-sensing nuclear receptors PPAR (α, γ, β/δ): HTVS and molecular docking/dynamics analysis of pharmacological ligands as potential pan-PPAR agonists.Molecular diversity · 2024Article
- Nrf2 Signaling Pathway as a Key to Treatment for Diabetic Dyslipidemia and Atherosclerosis.International journal of molecular sciences · 2024Review
- Fibroblast growth factor 21: An emerging pleiotropic regulator of lipid metabolism and the metabolic network.Genes & diseases · 2024Review
9 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 9 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe very low-density lipoprotein receptor (VLDLR) plays an important role in the development of hepatic steatosis. In this study, we investigated the role of Peroxisome Proliferator-Activated Receptor (PPAR)β/δ and fibroblast growth factor 21 (FGF21) in hepatic VLDLR regulation.
methodsStudies were conducted in wild-type and Pparβ/δ-null mice, primary mouse hepatocytes, human Huh-7 hepatocytes, and liver biopsies from control subjects and patients with moderate and severe hepatic steatosis.
resultsIncreased VLDLR levels were observed in liver of Pparβ/δ-null mice and in Pparβ/δ-knocked down mouse primary hepatocytes through mechanisms involving the heme-regulated eukaryotic translation initiation factor 2α (eIF2α) kinase (HRI), activating transcription factor (ATF) 4 and the oxidative stress-induced nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathways. Moreover, by using a neutralizing antibody against FGF21, Fgf21-null mice and by treating mice with recombinant FGF21, we show that FGF21 may protect against hepatic steatosis by attenuating endoplasmic reticulum (ER) stress-induced VLDLR upregulation. Finally, in liver biopsies from patients with moderate and severe hepatic steatosis, we observed an increase in VLDLR levels that was accompanied by a reduction in PPARβ/δ mRNA abundance and DNA-binding activity compared with control subjects.
conclusionsOverall, these findings provide new mechanisms by which PPARβ/δ and FGF21 regulate VLDLR levels and influence hepatic steatosis development.
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