ArticleExperimental neurology2017
Regulation of brain PPARgamma2 contributes to ketogenic diet anti-seizure efficacy.
Article in Experimental neurology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 91 citations in OpenAlex.
- Healing from the Ocean: Targeting Shared Mechanisms in Autism and Epilepsy Using Algae-Derived Compounds.Marine drugs · 2026Review
- Review
- The significance of the ketolytic gene OXCT1 in metabolism, intracellular signaling and disease development.Cellular and molecular life sciences : CMLS · 2026Review
- Hydroxycarboxylic Acid Receptor 2 Mediates β-hydroxybutyrate's Antiseizure Effect in Mice.Annals of neurology · 2026Article
- Fenofibrate as a PPARα Agonist Modulates Neuroinflammation and Glutamate Receptors in a Rat Model of Temporal Lobe Epilepsy: Region-Specific Effects and Behavioral Outcomes.International journal of molecular sciences · 2025Article
- Article
- The hydroxycarboxylic acid receptor HCA2 is required for the protective effect of ketogenic diet in epilepsy.Pharmacology research & perspectives · 2024Article
- PPARβ/δ Agonist GW0742 Modulates Microglial and Astroglial Gene Expression in a Rat Model of Temporal Lobe Epilepsy.International journal of molecular sciences · 2024Article
- Cannabidiol ameliorates mitochondrial disease via PPARγ activation in preclinical models.Nature communications · 2024Article
- The Role of Circadian Rhythm in Neurological Diseases: A Translational Perspective.Aging and disease · 2024Review
- Efficacy and safety of modified medium-chain triglyceride ketogenic diet in patients with drug-resistant epilepsy.Acta epileptologica · 2024Article
- Review
- Association of dietary decanoic acid intake with diabetes or prediabetes: an analysis from NHANES 2005-2016.Frontiers in nutrition · 2024Article
- Decreased neuronal excitability in hypertriglyceridemia hamsters with acute seizures.Frontiers in neurology · 2024Article
- A Potential Role for the Ketogenic Diet in Alzheimer's Disease Treatment: Exploring Pre-Clinical and Clinical Evidence.Metabolites · 2023Review
- Glioblastomas: Hijacking Metabolism to Build a Flexible Shield for Therapy Resistance.Antioxidants & redox signaling · 2023Review
- Beneficial Effects of ProbioticInternational journal of molecular sciences · 2023Article
- Hepatokines, bile acids and ketone bodies are novel Hormones regulating energy homeostasis.Frontiers in endocrinology · 2023Review
- The metabolic basis of epilepsy.Nature reviews. Neurology · 2022Review
- Updates on the ketogenic diet therapy for pediatric epilepsy.Biomedical journal · 2022Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The ketogenic diet (KD) is an effective therapy primarily used in pediatric patients whom are refractory to current anti-seizure medications. The mechanism of the KD is not completely understood, but is thought to involve anti-inflammatory and anti-oxidant processes. The nutritionally-regulated transcription factor peroxisome proliferator activated receptor gamma, PPARγ, regulates genes involved in anti-inflammatory and anti-oxidant pathways. Moreover, endogenous ligands of PPARγ include fatty acids suggesting a potential role in the effects of the KD. Here, we tested the hypothesis that PPARγ contributes to the anti-seizure efficacy of the KD. We found that the KD increased nuclear protein content of the PPARγ2 splice variant by 2-4 fold (P<0.05) in brain homogenates from wild-type (WT) and epileptic Kv1.1 knockout (KO) mice, while not affecting PPARγ1. The KD reduced the frequency of seizures in Kv1.1KO mice by ~70% (P<0.01). GW9662, a PPARγ antagonist, prevented KD-mediated changes in PPARγ2 expression and prevented the anti-seizure efficacy of the KD in Kv1.1KO mice. Further supporting the association of PPARγ2 in mediating KD actions, the KD significantly prolonged the latency to flurothyl-induced seizure in WT mice by ~20-35% (P<0.01), but was ineffective in PPARγ2KO mice and neuron-specific PPARγKO mice. Finally, administering the PPARγ agonist pioglitazone increased PPARγ2 expression by 2-fold (P<0.01) and reduced seizures in Kv1.1KO mice by ~80% (P<0.01). Our findings implicate brain PPARγ2 among the mechanisms by which the KD reduces seizures and strongly support the development of PPARγ2 as a therapeutic target for severe, refractory epilepsy.
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