ArticleAmerican journal of physiology. Endocrinology and metabolism2014
Impairments of hepatic gluconeogenesis and ketogenesis in PPARα-deficient neonatal mice.
Article in American journal of physiology. Endocrinology and metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- Cardioprotective Effects of 1,3 Butanediol in MASLD via Reversal of Cardiac Lipid Accumulation and Suppression of Cardiac Fibrosis.International journal of molecular sciences · 2026Article
- RNF128 regulates the adaptive metabolic response to fasting by modulating PPARα function.Cell death and differentiation · 2026Article
- Cold exposure-inducedActa pharmaceutica Sinica. B · 2026Article
- Current Understanding of Bovine Ketosis: From Molecular Basis to Farm-Level Management.Animals : an open access journal from MDPI · 2025Review
- Ketogenic Nutrition in Combination With PPARα Activation Induced Metabolic Failure and Exacerbated Muscle Weakness in Septic Mice.Journal of cachexia, sarcopenia and muscle · 2025Article
- Article
- Intestinal gluconeogenesis controls the neonatal development of hypothalamic feeding circuits.Molecular metabolism · 2024Article
- Targeting ketone body metabolism to treat fatty liver disease.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2024Review
- Adipokines in glucose and lipid metabolism.Adipocyte · 2023Article
- Article
- Interactions between nuclear receptors glucocorticoid receptor α and peroxisome proliferator-activated receptor α form a negative feedback loop.Reviews in endocrine & metabolic disorders · 2022Review
- Bittersweet: relevant amounts of the common sweet food additive, glycerol, accelerate the growth of PC3 human prostate cancer xenografts.BMC research notes · 2022Article
- β-Hydroxybutyrate in Cardiovascular Diseases : A Minor Metabolite of Great Expectations.Frontiers in molecular biosciences · 2022Review
- Emerging Role of Hepatic Ketogenesis in Fatty Liver Disease.Frontiers in physiology · 2022Review
- The Beneficial Effects of Principal Polyphenols from Green Tea, Coffee, Wine, and Curry on Obesity.Molecules (Basel, Switzerland) · 2021Review
- CDKN2A/p16INK4a suppresses hepatic fatty acid oxidation through the AMPKα2-SIRT1-PPARα signaling pathway.The Journal of biological chemistry · 2020Article
- β-Hydroxybutyrate is reduced in humans with obesity-related NAFLD and displays a dose-dependent effect on skeletal muscle mitochondrial respiration in vitro.American journal of physiology. Endocrinology and metabolism · 2020Article
- Hepatocyte-specific deletion of Pparα promotes NAFLD in the context of obesity.Scientific reports · 2020Article
- PPARα augments heart function and cardiac fatty acid oxidation in early experimental polymicrobial sepsis.American journal of physiology. Heart and circulatory physiology · 2017Article
- Glucocorticoid receptor-PPARα axis in fetal mouse liver prepares neonates for milk lipid catabolism.eLife · 2016Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Peroxisome proliferator activated receptor-α (PPARα) is a master transcriptional regulator of hepatic metabolism and mediates the adaptive response to fasting. Here, we demonstrate the roles for PPARα in hepatic metabolic adaptations to birth. Like fasting, nutrient supply is abruptly altered at birth when a transplacental source of carbohydrates is replaced by a high-fat, low-carbohydrate milk diet. PPARα-knockout (KO) neonatal mice exhibit relative hypoglycemia due to impaired conversion of glycerol to glucose. Although hepatic expression of fatty acyl-CoA dehydrogenases is imparied in PPARα neonates, these animals exhibit normal blood acylcarnitine profiles. Furthermore, quantitative metabolic fate mapping of the medium-chain fatty acid [(13)C]octanoate in neonatal mouse livers revealed normal contribution of this fatty acid to the hepatic TCA cycle. Interestingly, octanoate-derived carbon labeled glucose uniquely in livers of PPARα-KO neonates. Relative hypoketonemia in newborn PPARα-KO animals could be mechanistically linked to a 50% decrease in de novo hepatic ketogenesis from labeled octanoate. Decreased ketogenesis was associated with diminished mRNA and protein abundance of the fate-committing ketogenic enzyme mitochondrial 3-hydroxymethylglutaryl-CoA synthase (HMGCS2) and decreased protein abundance of the ketogenic enzyme β-hydroxybutyrate dehydrogenase 1 (BDH1). Finally, hepatic triglyceride and free fatty acid concentrations were increased 6.9- and 2.7-fold, respectively, in suckling PPARα-KO neonates. Together, these findings indicate a primary defect of gluconeogenesis from glycerol and an important role for PPARα-dependent ketogenesis in the disposal of hepatic fatty acids during the neonatal period.
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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.