ArticleThe Biochemical journal2011
Farnesyl pyrophosphate regulates adipocyte functions as an endogenous PPARγ agonist.
Article in The Biochemical journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Endothelial delivery of simvastatin by LRP1-targeted nanoparticles ameliorates pathogenesis of alzheimer's disease in a mouse model.Alzheimer's research & therapy · 2025Article
- Cardiac maturation.Journal of molecular and cellular cardiology · 2024Review
- GPR92 activation in islet macrophages controls β cell function in a diet-induced obesity model.The Journal of clinical investigation · 2022Article
- Statins reduce castration-induced bone marrow adiposity and prostate cancer progression in bone.Oncogene · 2021Article
- Integrated Proteomics and Metabolomics Analysis of Perirenal Adipose Tissue in Obese Rabbits Treated with a Restricted Diet.Biology · 2021Article
- Dysregulation of the mevalonate pathway during SARS-CoV-2 infection: An in silico study.Journal of medical virology · 2021Article
- Article
- Suksdorfin Promotes Adipocyte Differentiation and Improves Abnormalities in Glucose Metabolism via PPARγ Activation.Lipids · 2017Article
- The hepatokine FGF21 is crucial for peroxisome proliferator-activated receptor-α agonist-induced amelioration of metabolic disorders in obese mice.The Journal of biological chemistry · 2017Article
- Differential Regulation of Gene Expression by Cholesterol Biosynthesis Inhibitors That Reduce (Pravastatin) or Enhance (Squalestatin 1) Nonsterol Isoprenoid Levels in Primary Cultured Mouse and Rat Hepatocytes.The Journal of pharmacology and experimental therapeutics · 2016Article
- Nonsterol Isoprenoids Activate Human Constitutive Androstane Receptor in an Isoform-Selective Manner in Primary Cultured Mouse Hepatocytes.Drug metabolism and disposition: the biological fate of chemicals · 2016Article
- Trans, trans-farnesol as a mevalonate-derived inducer of murine 3T3-F442A pre-adipocyte differentiation.Experimental biology and medicine (Maywood, N.J.) · 2016Article
- Transcriptional Regulation of Cytosolic Sulfotransferase 1C2 by Intermediates of the Cholesterol Biosynthetic Pathway in Primary Cultured Rat Hepatocytes.The Journal of pharmacology and experimental therapeutics · 2015Article
- Gamma-tocotrienol attenuates high-fat diet-induced obesity and insulin resistance by inhibiting adipose inflammation and M1 macrophage recruitment.International journal of obesity (2005) · 2015Article
- Metabolomics reveal 1-palmitoyl lysophosphatidylcholine production by peroxisome proliferator-activated receptor α.Journal of lipid research · 2015Article
- 13-Oxo-9(Z),11(E),15(Z)-octadecatrienoic acid activates peroxisome proliferator-activated receptor γ in adipocytes.Lipids · 2015Article
- Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARγ): a review.Biochemical pharmacology · 2014Review
- Integrated analysis of transcript-level regulation of metabolism reveals disease-relevant nodes of the human metabolic network.Nucleic acids research · 2014Article
- CMHX008, a novel peroxisome proliferator-activated receptor γ partial agonist, enhances insulin sensitivity in vitro and in vivo.PloS one · 2014Article
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13 authors.
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No grant is acknowledged in the PubMed record.
Abstract
The cholesterol biosynthetic pathway produces not only sterols but also non-sterol mevalonate metabolites involved in isoprenoid synthesis. Mevalonate metabolites affect transcriptional and post-transcriptional events that in turn affect various biological processes including energy metabolism. In the present study, we examine whether mevalonate metabolites activate PPARγ (peroxisome-proliferator-activated receptor γ), a ligand-dependent transcription factor playing a central role in adipocyte differentiation. In the luciferase reporter assay using both GAL4 chimaera and full-length PPARγ systems, a mevalonate metabolite, FPP (farnesyl pyrophosphate), which is the precursor of almost all isoprenoids and is positioned at branch points leading to the synthesis of other longer-chain isoprenoids, activated PPARγ in a dose-dependent manner. FPP induced the in vitro binding of a co-activator, SRC-1 (steroid receptor co-activator-1), to GST (glutathione transferase)-PPARγ. Direct binding of FPP to PPARγ was also indicated by docking simulation studies. Moreover, the addition of FPP up-regulated the mRNA expression levels of PPARγ target genes during adipocyte differentiation induction. In the presence of lovastatin, an HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase inhibitor, both intracellular FPP levels and PPARγ-target gene expressions were decreased. In contrast, the increase in intracellular FPP level after the addition of zaragozic acid, a squalene synthase inhibitor, induced PPARγ-target gene expression. The addition of FPP and zaragozic acid promotes lipid accumulation during adipocyte differentiation. These findings indicated that FPP might function as an endogenous PPARγ agonist and regulate gene expression in adipocytes.
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