ArticleMolecular pharmacology2014
Valproic acid is a novel activator of AMP-activated protein kinase and decreases liver mass, hepatic fat accumulation, and serum glucose in obese mice.
Article in Molecular pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 57 citations in OpenAlex.
- The Role of Sodium Valproate in Clozapine-Associated Cardiotoxicities: The Importance of Cellular and Systemic Energetics.Cardiovascular toxicology · 2026Review
- Innovative Therapeutic Approaches Targeting Obesity: Can Flavonoids Improve the Efficacy of Anti-Obesogenic Drugs?International journal of molecular sciences · 2025Review
- Valproate independently activates Snf1, inhibits TORC1, and induces repression of INO1 transcription by increasing nuclear localization of Opi1.Scientific reports · 2025Article
- Mechanisms Underlying the Protective Effects of Obeticholic Acid-activated FXR in Valproic Acid-induced HepatotoxicityCurrent computer-aided drug design · 2025Article
- Histone deacetylase inhibitors VPA and WT161 ameliorate the pathological features and cognitive impairments of the APP/PS1 Alzheimer's disease mouse model by regulating the expression of APP secretases.Alzheimer's research & therapy · 2024Article
- CaMKK2 as an emerging treatment target for bipolar disorder.Molecular psychiatry · 2023Review
- Anticonvulsant Profile of Selected Medium-Chain Fatty Acids (MCFAs) Co-Administered with Metformin in Mice in Acute and Chronic Treatment.Molecules (Basel, Switzerland) · 2023Article
- Association of epilepsy, anti-epileptic drugs (AEDs), and type 2 diabetes mellitus (T2DM): a population-based cohort retrospective study, impact of AEDs on T2DM-related molecular pathway, and via peroxisome proliferator-activated receptor γ transactivation.Frontiers in endocrinology · 2023Article
- Alterations in Cerebellar Microtubule Cytoskeletal Network in a ValproicAcid-Induced Rat Model of Autism Spectrum Disorders.Biomedicines · 2022Article
- Integrative genomics reveals pathogenic mediator of valproate-induced neurodevelopmental disability.Brain : a journal of neurology · 2022Article
- C/EBPα regulates the fate of bone marrow mesenchymal stem cells and steroid-induced avascular necrosis of the femoral head by targeting the PPARγ signalling pathway.Stem cell research & therapy · 2022Article
- An Overview of Epigenetics in Obesity: The Role of Lifestyle and Therapeutic Interventions.International journal of molecular sciences · 2022Review
- Epigenetic Small-Molecule Modulators Targeting Metabolic Pathways in Cancer.Sub-cellular biochemistry · 2022Article
- Valproic Acid: A Potential Therapeutic for Spinal Cord Injury.Cellular and molecular neurobiology · 2021Review
- Valproic acid influences the expression of genes implicated with hyperglycaemia-induced complement and coagulation pathways.Scientific reports · 2021Article
- The Role of HDACs and HDACi in Cartilage and Osteoarthritis.Frontiers in cell and developmental biology · 2020Review
- Nutritional Factors, DNA Methylation, and Risk of Type 2 Diabetes and Obesity: Perspectives and Challenges.International journal of molecular sciences · 2019Review
- HDAC (Histone Deacetylase) Inhibitor Valproic Acid Attenuates Atrial Remodeling and Delays the Onset of Atrial Fibrillation in Mice.Circulation. Arrhythmia and electrophysiology · 2019Article
- Metabolic and Epigenetic Action Mechanisms of Antidiabetic Medicinal Plants.Evidence-based complementary and alternative medicine : eCAM · 2019Review
- Epigenetic regulation of melatonin receptors in neuropsychiatric disorders.British journal of pharmacology · 2018Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Valproic acid (VPA) is a widely prescribed anticonvulsant for the treatment of epilepsy. Here we demonstrate that VPA is a novel activator of AMP-activated protein kinase (AMPK), a key regulator of cellular metabolism, using primary mouse and human hepatocytes. Incubation of primary mouse hepatocytes with VPA resulted in increased levels of phosphorylated AMPK and acetyl-CoA carboxylase (ACC). This finding was recapitulated using primary human hepatocytes. Pretreatment of mouse hepatocytes with a small-molecule inhibitor of AMPK, Compound C (6-[4-(2-piperidin-1-ylethoxy)phenyl]-3-pyridin-4-ylpyrazolo[1,5-a]pyrimidine), abrogated the phosphorylation of ACC following treatment with VPA. The cytochrome P450 inhibitor 1-aminobenzotriazole blocked the VPA-stimulated phosphorylation of AMPK, suggesting a requirement for biotransformation of VPA. In line with this, treatment of hepatocytes with metabolites of VPA resulted in increased phosphorylation of AMPK/ACC as compared with VPA. Treatment of ob/ob mice with VPA for 14 days resulted in decreased liver masses, hepatic fat accumulation, and serum glucose. These results paralleled those observed in mice treated with metformin. In addition, a targeted mass spectrometry-based metabolomics assay revealed several small molecules that were differentially abundant in the serum of ob/ob mice treated with VPA as compared with vehicle-treated mice. These studies are the first to establish VPA and its metabolites as in vitro activators of AMPK.
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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.