ArticleMolecular endocrinology (Baltimore, Md.)2015
Ketone Body Therapy Protects From Lipotoxicity and Acute Liver Failure Upon Pparα Deficiency.
Article in Molecular endocrinology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
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- Understanding Diabetic Cardiomyopathy: Insulin Resistance and Beyond.Heart international · 2024Review
- β-hydroxybutyrate administration improves liver injury and metabolic abnormality in postnatal growth retardation piglets.Frontiers in veterinary science · 2023Article
- Unraveling and Targeting Myocardial Regeneration Deficit in Diabetes.Antioxidants (Basel, Switzerland) · 2022Review
- β-Hydroxybutyrate in Cardiovascular Diseases : A Minor Metabolite of Great Expectations.Frontiers in molecular biosciences · 2022Review
- Article
- Jekyll and Hyde: nuclear receptors ignite and extinguish hepatic oxidative milieu.Trends in endocrinology and metabolism: TEM · 2021Review
- The Mystery of Diabetic Cardiomyopathy: From Early Concepts and Underlying Mechanisms to Novel Therapeutic Possibilities.International journal of molecular sciences · 2021Review
- Impact of peroxisome proliferator-activated receptor-α on diabetic cardiomyopathy.Cardiovascular diabetology · 2021Review
- Review
- SGLT2 Inhibitors: A Novel Player in the Treatment and Prevention of Diabetic Cardiomyopathy.Drug design, development and therapy · 2020Review
- The Iconic Atlantic Goliath Grouper (Frontiers in veterinary science · 2020Article
- Nuclear magnetic resonance-based serum metabolomic analysis reveals different disease evolution profiles between septic shock survivors and non-survivors.Critical care (London, England) · 2019Article
- Hepatic PPARα is critical in the metabolic adaptation to sepsis.Journal of hepatology · 2019Article
- Alteration in gut microbiota caused by time-restricted feeding alleviate hepatic ischaemia reperfusion injury in mice.Journal of cellular and molecular medicine · 2019Article
- Hepatocyte-Macrophage Acetoacetate Shuttle Protects against Tissue Fibrosis.Cell metabolism · 2019Article
- Diabetic Cardiomyopathy: An Update of Mechanisms Contributing to This Clinical Entity.Circulation research · 2018Review
- The logic of transcriptional regulator recruitment architecture atGenome research · 2017Article
- Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics.Cell metabolism · 2017Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute liver failure (ALF) is a severe and rapid liver injury, often occurring without any preexisting liver disease, which may precipitate multiorgan failure and death. ALF is often associated with impaired β-oxidation and increased oxidative stress (OS), characterized by elevated levels of hepatic reactive oxygen species (ROS) and lipid peroxidation (LPO) products. Peroxisome proliferator-activated receptor (PPAR)α has been shown to confer hepatoprotection in acute and chronic liver injury, at least in part, related to its ability to control peroxisomal and mitochondrial β-oxidation. To study the pathophysiological role of PPARα in hepatic response to high OS, we induced a pronounced LPO by treating wild-type and Pparα-deficient mice with high doses of fish oil (FO), containing n-3 polyunsaturated fatty acids. FO feeding of Pparα-deficient mice, in contrast to control sunflower oil, surprisingly induced coma and death due to ALF as indicated by elevated serum alanine aminotransferase, aspartate aminotransferase, ammonia, and a liver-specific increase of ROS and LPO-derived malondialdehyde. Reconstitution of PPARα specifically in the liver using adeno-associated serotype 8 virus-PPARα in Pparα-deficient mice restored β-oxidation and ketogenesis and protected mice from FO-induced lipotoxicity and death. Interestingly, administration of the ketone body β-hydroxybutyrate prevented FO-induced ALF in Pparα-deficient mice, and normalized liver ROS and malondialdehyde levels. Therefore, PPARα protects the liver from FO-induced OS through its regulatory actions on ketone body levels. β-Hydroxybutyrate treatment could thus be an option to prevent LPO-induced liver damage.
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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.