Details

Autor(en) / Beteiligte

• Lin, Lin
• Mabou Tagne, Alex
• Squire, Erica N.
• Lee, Hye-Lim
• Fotio, Yannick
• Ramirez, Jade
• Zheng, Mimi
• Torrens, Alexa
• Ahmed, Faizy
• Ramos, Raul
• Plikus, Maksim V.
• Piomelli, Daniele

Titel

Diet-Induced Obesity Disrupts Histamine-Dependent Oleoylethanolamide Signaling in the Mouse Liver

Ist Teil von

• Pharmacology, 2022-07, Vol.107 (7-8), p.423-432

Ort / Verlag

Basel, Switzerland: S. Karger AG

Erscheinungsjahr

2022

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Introduction: Previous work suggests the existence of a paracrine signaling mechanism in which histamine released from visceral mast cells into the portal circulation contributes to fasting-induced ketogenesis by stimulating biosynthesis of the endogenous high-affinity PPAR-α agonist oleoylethanolamide (OEA). Methods: Male C57Bl/6J mice were rendered obese by exposure to a high-fat diet (HFD; 60% fat). We measured histamine, OEA, and other fatty-acid ethanolamides by liquid-chromatography/mass spectrometry, gene transcription by RT-PCR, protein expression by ELISA, neutral lipid accumulation in the liver using Red Oil O and BODIPY staining, and collagen levels using picrosirius red staining. Results: Long-term exposure to HFD suppressed both fasting-induced histamine release into portal blood and histamine-dependent OEA production in the liver. Additionally, subchronic OEA administration reduced lipid accumulation, inflammatory responses, and fibrosis in the liver of HFD-exposed mice. Discussion: The results suggest that disruption of histamine-dependent OEA signaling in the liver might contribute to pathology in obesity-associated liver steatosis.