ArticleMolecular and cellular biology2009
Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) but not PPARalpha serves as a plasma free fatty acid sensor in liver.
Article in Molecular and cellular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 75 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
75 citing papers in PubMed, 1 synthesis or guideline pooled it, 142 citations in OpenAlex.
- Mixed modeling of meta-analysis P-values (MixMAP) suggests multiple novel gene loci for low density lipoprotein cholesterol.PloS one · 2013Pooled it
- Spillover of Fatty acids during dietary fat storage in type 2 diabetes: relationship to body fat depots and effects of weight loss.Diabetes · 2013Trial
- Omega-3 long-chain fatty acids strongly induce angiopoietin-like 4 in humans.Journal of lipid research · 2013Trial
- Pronounced effects of acute endurance exercise on gene expression in resting and exercising human skeletal muscle.PloS one · 2012Trial
- The central benefit of physiologically induced ketogenic states.The Journal of physiology · 2026Review
- ANGPTL4: A Comprehensive Review of 25 Years of Research.Cancers · 2025Review
- Selective PPARα Modulator (SPPARMα) in the Era of the MASLD Pandemic: Current Insights and Future Prospects.Yonago acta medica · 2025Review
- Role of PNPLA3 in Hepatic Stellate Cells and Hepatic Cellular Crosstalk.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Overview of Ursolic Acid Potential for the Treatment of Metabolic Disorders, Autoimmune Diseases, and Cancers via Nuclear Receptor Pathways.Biomedicines · 2023Review
- Harnessing Oleanolic Acid and Its Derivatives as Modulators of Metabolic Nuclear Receptors.Biomolecules · 2023Review
- Ligand dependent interaction between PC-TP and PPARδ mitigates diet-induced hepatic steatosis in male mice.Nature communications · 2023Article
- A Network Pharmacology Study on the Active Components and Targets of the Radix Ginseng and Radix Bupleuri Herb Pair for Treating Nonalcoholic Fatty Liver Disease.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- The transcription factors CREBH, PPARa, and FOXO1 as critical hepatic mediators of diet-induced metabolic dysregulation.The Journal of nutritional biochemistry · 2021Review
- Celastrol Prevents Oxidative Stress Effects on FSHR, PAPP, and CYP19A1 Gene Expression in Cultured Human Granulosa-Lutein Cells.International journal of molecular sciences · 2021Article
- The Hepatotoxicity of Alantolactone and Germacrone: Their Influence on Cholesterol and Lipid Metabolism in Differentiated HepaRG Cells.Nutrients · 2020Article
- The interplay between non-esterified fatty acids and bovine peroxisome proliferator-activated receptors: results of anJournal of animal science and biotechnology · 2020Article
- Metabolic flux analyses to assess the differentiation of adult cardiac progenitors after fatty acid supplementation.Stem cell research · 2019Article
- MicroRNA-382 silencing induces a mitonuclear protein imbalance and activates the mitochondrial unfolded protein response in muscle cells.Journal of cellular physiology · 2019Article
- Kynurenine 3-Monooxygenase Activity in Human Primary Neurons and Effect on Cellular Bioenergetics Identifies New Neurotoxic Mechanisms.Neurotoxicity research · 2019Article
- Mechanism of Action of Magnesium Lithospermate B against Aging and Obesity-Induced ER Stress, Insulin Resistance, and Inflammsome Formation in the Liver.Molecules (Basel, Switzerland) · 2018Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Peroxisome proliferator-activated receptor alpha (PPARalpha) is an important transcription factor in liver that can be activated physiologically by fasting or pharmacologically by using high-affinity synthetic agonists. Here we initially set out to elucidate the similarities in gene induction between Wy14643 and fasting. Numerous genes were commonly regulated in liver between the two treatments, including many classical PPARalpha target genes, such as Aldh3a2 and Cpt2. Remarkably, several genes induced by Wy14643 were upregulated by fasting independently of PPARalpha, including Lpin2 and St3gal5, suggesting involvement of another transcription factor. Using chromatin immunoprecipitation, Lpin2 and St3gal5 were shown to be direct targets of PPARbeta/delta during fasting, whereas Aldh3a2 and Cpt2 were exclusive targets of PPARalpha. Binding of PPARbeta/delta to the Lpin2 and St3gal5 genes followed the plasma free fatty acid (FFA) concentration, consistent with activation of PPARbeta/delta by plasma FFAs. Subsequent experiments using transgenic and knockout mice for Angptl4, a potent stimulant of adipose tissue lipolysis, confirmed the stimulatory effect of plasma FFAs on Lpin2 and St3gal5 expression levels via PPARbeta/delta. In contrast, the data did not support activation of PPARalpha by plasma FFAs. The results identify Lpin2 and St3gal5 as novel PPARbeta/delta target genes and show that upregulation of gene expression by PPARbeta/delta is sensitive to plasma FFA levels. In contrast, this is not the case for PPARalpha, revealing a novel mechanism for functional differentiation between PPARs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.