ArticleProceedings of the National Academy of Sciences of the United States of America1999
A critical role for the peroxisome proliferator-activated receptor alpha (PPARalpha) in the cellular fasting response: the PPARalpha-null mouse as a model of fatty acid oxidation disorders.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 374 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
374 citing papers in PubMed, 1 synthesis or guideline pooled it, 936 citations in OpenAlex.
- Pooled it
- Prolonged fasting-induced metabolic signatures in human skeletal muscle of lean and obese men.PloS one · 2018Trial
- A somatic checkpoint through NHR-49/HNF4α governs reproductive investment and longevity in C. elegans.Nature communications · 2026Article
- A membrane homeostatic response to lipid overload coordinates fatty acid metabolism.bioRxiv : the preprint server for biology · 2026Article
- METTL14 inhibits atherogenesis by epigenetically activating PPAR-α/γ transcription and fatty acid oxidation in VSMCs.Cardiovascular research · 2026Article
- Exploring the Cardioprotective Spectrum-Effect Relationship ofPharmaceuticals (Basel, Switzerland) · 2026Article
- PPARα: Linking Cardiac Metabolism to Therapeutic Opportunities in Cardiovascular Diseases.Cells · 2026Review
- Roles of ubiquitin‑specific peptidase 22 in cellular fate: From embryonic survival to tissue repair, inflammation and metabolism (Review).International journal of molecular medicine · 2026Review
- Protein turnover downstream of the Nipbl/CRL4 axis contributes to abnormal development in zebrafish embryos.Developmental dynamics : an official publication of the American Association of Anatomists · 2026Article
- The Function of PPARα in Cancer Drug Development: A Promising Target for Cancer Treatment.Current cancer drug targets · 2026Review
- A Critical Assessment of Fasting to Promote Metabolic Health and Longevity.Endocrine reviews · 2025Review
- Caloric Restriction Enhances the Efficacy of Antiandrogen Therapy in Prostate Cancer by Inhibiting Androgen Receptor Translation.Cancer research · 2025Article
- The ribonucleoprotein hnRNP K promotes hepatic steatosis by suppressing the nuclear hormone receptor PPARα.The Journal of biological chemistry · 2025Article
- Liver Metabolism at the Crossroads: The Reciprocal Control of Nutrient-Sensing Nuclear Receptors and Autophagy.International journal of molecular sciences · 2025Review
- Wogonin Attenuates Atherosclerosis via KLF11-Mediated Suppression of PPARα-YAP1-Driven Glycolysis and Enhancement of ABCA1/G1-Mediated Cholesterol Efflux.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Unraveling the metabolic gene expression and energetic patterns of the seasonally acclimatized gilthead seabream.Fish physiology and biochemistry · 2025Article
- PPARα regulates ER-lipid droplet protein Calsyntenin-3β to promote ketogenesis in hepatocytes.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- PPARα Genetic Deletion Reveals Global Transcriptional Changes in the Brain and Exacerbates Cerebral Infarction in a Mouse Model of Stroke.International journal of molecular sciences · 2025Article
- Plin5: A potential therapeutic target for type 2 diabetes mellitus.Diabetology & metabolic syndrome · 2025Article
- A decrease in Flavonifractor plautii and its product, phytosphingosine, predisposes individuals with phlegm-dampness constitution to metabolic disorders.Cell discovery · 2025Article
314 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
We hypothesized that the lipid-activated transcription factor, the peroxisome proliferator-activated receptor alpha (PPARalpha), plays a pivotal role in the cellular metabolic response to fasting. Short-term starvation caused hepatic steatosis, myocardial lipid accumulation, and hypoglycemia, with an inadequate ketogenic response in adult mice lacking PPARalpha (PPARalpha-/-), a phenotype that bears remarkable similarity to that of humans with genetic defects in mitochondrial fatty acid oxidation enzymes. In PPARalpha+/+ mice, fasting induced the hepatic and cardiac expression of PPARalpha target genes encoding key mitochondrial (medium-chain acyl-CoA dehydrogenase, carnitine palmitoyltransferase I) and extramitochondrial (acyl-CoA oxidase, cytochrome P450 4A3) enzymes. In striking contrast, the hepatic and cardiac expression of most PPARalpha target genes was not induced by fasting in PPARalpha-/- mice. These results define a critical role for PPARalpha in a transcriptional regulatory response to fasting and identify the PPARalpha-/- mouse as a potentially useful murine model of inborn and acquired abnormalities of human fatty acid utilization.
Indexed as
Identifiers
What OpenQuestion holds
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.