Regulation of Ketone Body Metabolism and the Role of PPARα

• Main Authors: Maja Grabacka, Malgorzata Pierzchalska, Matthew Dean, Krzysztof Reiss
• Format: Article
• Language: English
• Published: MDPI AG 2016-12-01
• Series: International Journal of Molecular Sciences
• Subjects: β hydroxybutyrate; 3-hydroxy-3-methylglytaryl-CoA synthetase 2 (HMGCS2); fenofibrate; melanoma; glioma; fasting
• Online Access: http://www.mdpi.com/1422-0067/17/12/2093

Ketogenesis and ketolysis are central metabolic processes activated during the response to fasting. Ketogenesis is regulated in multiple stages, and a nuclear receptor peroxisome proliferator activated receptor α (PPARα) is one of the key transcription factors taking part in this regulation. PPARα is an important element in the metabolic network, where it participates in signaling driven by the main nutrient sensors, such as AMP-activated protein kinase (AMPK), PPARγ coactivator 1α (PGC-1α), and mammalian (mechanistic) target of rapamycin (mTOR) and induces hormonal mediators, such as fibroblast growth factor 21 (FGF21). This work describes the regulation of ketogenesis and ketolysis in normal and malignant cells and briefly summarizes the positive effects of ketone bodies in various neuropathologic conditions.