| First Author | Misto A | Year | 2019 |
| Journal | Cell Metab | Volume | 29 |
| Issue | 1 | Pages | 91-102.e5 |
| PubMed ID | 30318340 | Mgi Jnum | J:273688 |
| Mgi Id | MGI:6282405 | Doi | 10.1016/j.cmet.2018.09.014 |
| Citation | Misto A, et al. (2019) Mast Cell-Derived Histamine Regulates Liver Ketogenesis via Oleoylethanolamide Signaling. Cell Metab 29(1):91-102.e5 |
| abstractText | The conversion of lipolysis-derived fatty acids into ketone bodies (ketogenesis) is a crucial metabolic adaptation to prolonged periods of food scarcity. The process occurs primarily in liver mitochondria and is initiated by fatty-acid-mediated stimulation of the ligand-operated transcription factor, peroxisome proliferator-activated receptor-alpha (PPAR-alpha). Here, we present evidence that mast cells contribute to the control of fasting-induced ketogenesis via a paracrine mechanism that involves secretion of histamine into the hepatic portal circulation, stimulation of liver H1 receptors, and local biosynthesis of the high-affinity PPAR-alpha agonist, oleoylethanolamide (OEA). Genetic or pharmacological interventions that disable any one of these events, including mast cell elimination, deletion of histamine- or OEA-synthesizing enzymes, and H1 blockade, blunt ketogenesis without affecting lipolysis. The results reveal an unexpected role for mast cells in the regulation of systemic fatty-acid homeostasis, and suggest that OEA may act in concert with lipolysis-derived fatty acids to activate liver PPAR-alpha and promote ketogenesis. |
