The ketogenic diet (KD) is an effective therapy for many patients with refractory epilepsy. It engages a wide array of antioxidant and anti-inflammatory processes and improves mitochondrial function, which is thought to underlie its neuroprotective, antiseizure, and disease-modifying effects. Potential roles of ketone bodies in these mechanisms are discussed elsewhere in this volume. This chapter focuses on the role of KD fatty acids as potential ligands for the nutritionally regulated nuclear transcription factor peroxisome proliferator activated receptor gamma (PPARgamma). PPARgamma regulates many of the pathways identified in the mechanism of the KD and, in recent years, has become a potential therapeutic target for neurodegenerative diseases. This chapter reviews what is known concerning PPARgamma in the brain, the evidence that PPARgamma has neuroprotective and antiseizure properties, and the evidence suggesting that PPARgamma may be involved in the antiseizure mechanisms of the ketogenic diet.
Peroxisome proliferator-activated receptor alpha and the ketogenic diet
