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Updated: Sep 8, 2025
Optimized Analysis of In Vivo and In Vitro Hepatic Steatosis
Published on: March 11, 2017
Diet-Induced Obesity Disrupts Histamine-Dependent Oleoylethanolamide Signaling in the Mouse Liver
Lin Lin1, Alex Mabou Tagne1, Erica N Squire1
1Department of Anatomy and Neurobiology, University of California, Irvine, California, USA.
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.
