%0 Journal Article
%T Diet-Induced Obesity Disrupts Histamine-Dependent Oleoylethanolamide Signaling in the Mouse Liver.
%A Lin L
%A Mabou Tagne A
%A Squire EN
%A Lee HL
%A Fotio Y
%A Ramirez J
%A Zheng M
%A Torrens A
%A Ahmed F
%A Ramos R
%A Plikus MV
%A Piomelli D
%A Lin L
%A Mabou Tagne A
%A Squire EN
%A Lee HL
%A Fotio Y
%A Ramirez J
%A Zheng M
%A Torrens A
%A Ahmed F
%A Ramos R
%A Plikus MV
%A Piomelli D
%A Lin L
%A Mabou Tagne A
%A Squire EN
%A Lee HL
%A Fotio Y
%A Ramirez J
%A Zheng M
%A Torrens A
%A Ahmed F
%A Ramos R
%A Plikus MV
%A Piomelli D
%J Pharmacology
%V 107
%N 7
%D 2022
%M 35691287
%F 3.429
%R 10.1159/000524753
%X <B>BACKGROUND: </B>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).<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>The results suggest that disruption of histamine-dependent OEA signaling in the liver might contribute to pathology in obesity-associated liver steatosis.