ArticleThe Journal of clinical investigation1999
Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting.
Article in The Journal of clinical investigation, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 651 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
651 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,632 citations in OpenAlex.
- The add-on effects of Danhong injection among patients with ischemic stroke receiving Western medicines: A systematic review and meta-analysis.Frontiers in pharmacology · 2022Pooled it
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- Disentangling microbiota-dependent and -independent impacts of antibiotics on host physiology.Nature microbiology · 2026Article
- Adrenal hormones in the maintenance of glucose homeostasis during prolonged fasting in male glucagon-deficient mice.Journal of diabetes investigation · 2026Article
- Lipoprotein biology during induced oogenesis in the short-finned eel, Anguilla australis-hepatic target gene expression and accumulation of nutrient sources into developing oocytes.Fish physiology and biochemistry · 2026Article
- Autoinhibition of untimely DNA binding by structural disorder in the full-length peroxisome proliferator-activated receptors (PPARs).Nature communications · 2026Article
- A somatic checkpoint through NHR-49/HNF4α governs reproductive investment and longevity in C. elegans.Nature communications · 2026Article
- Article
- Identification of Peroxisome Proliferator-Activated Receptors as Novel Regulators of Bovine Hepcidin Expression.Biochemical genetics · 2026Article
- A membrane homeostatic response to lipid overload coordinates fatty acid metabolism.bioRxiv : the preprint server for biology · 2026Article
- Transcriptomic Insights into Micro- and Nanoplastic Toxicity in Zebrafish: A Narrative Review.Toxics · 2026Review
- Hemp Seed Protein-Derived Lipase Inhibitory Peptides Attenuate High-Fat Diet-Induced Obesity: Evidence from Intestinal Fat Digestion and Gut-Liver Axis Regulation.Foods (Basel, Switzerland) · 2026Article
- Adiponectin exerts sex-dependent effects on lipid, amino acid, and glucose metabolism during caloric restriction.PLoS biology · 2026Article
- Hepatic FGF21 is not required for fasting metabolism but guides protein appetite post energy depletion.EMBO reports · 2026Article
- Comparative Hepatic Transcriptomic Analysis Reveals Metabolic Regulatory Differences Between Qilian and Oula Sheep.Veterinary sciences · 2026Article
- Molecular heterogeneity and differential metabolic signatures in thymic adipocytes.bioRxiv : the preprint server for biology · 2026Article
- Vitamin D as a Regulator of the Biological Clock-Implications for Circadian-Metabolic Dysregulation.International journal of molecular sciences · 2026Review
- Peroxisome proliferator‑activated receptor α regulates acesulfame‑K‑induced NAFLD via hepatic PLCβ: Foe and friend.International journal of molecular medicine · 2026Article
- Bilirubin Ameliorates Oleic and Palmitic Acid Accumulation in an In Vitro Model of MASLD.Physiological research · 2026Article
- RNF128 regulates the adaptive metabolic response to fasting by modulating PPARα function.Cell death and differentiation · 2026Article
591 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
6 authors at 4 institutions in 3 countries.
Funding
Abstract
Prolonged deprivation of food induces dramatic changes in mammalian metabolism, including the release of large amounts of fatty acids from the adipose tissue, followed by their oxidation in the liver. The nuclear receptor known as peroxisome proliferator-activated receptor alpha (PPARalpha) was found to play a role in regulating mitochondrial and peroxisomal fatty acid oxidation, suggesting that PPARalpha may be involved in the transcriptional response to fasting. To investigate this possibility, PPARalpha-null mice were subjected to a high fat diet or to fasting, and their responses were compared with those of wild-type mice. PPARalpha-null mice chronically fed a high fat diet showed a massive accumulation of lipid in their livers. A similar phenotype was noted in PPARalpha-null mice fasted for 24 hours, who also displayed severe hypoglycemia, hypoketonemia, hypothermia, and elevated plasma free fatty acid levels, indicating a dramatic inhibition of fatty acid uptake and oxidation. It is shown that to accommodate the increased requirement for hepatic fatty acid oxidation, PPARalpha mRNA is induced during fasting in wild-type mice. The data indicate that PPARalpha plays a pivotal role in the management of energy stores during fasting. By modulating gene expression, PPARalpha stimulates hepatic fatty acid oxidation to supply substrates that can be metabolized by other tissues.
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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.