{Reference Type}: Journal Article
{Title}: Diet-Induced Obesity Disrupts Histamine-Dependent Oleoylethanolamide Signaling in the Mouse Liver.
{Author}: Lin L;Mabou Tagne A;Squire EN;Lee HL;Fotio Y;Ramirez J;Zheng M;Torrens A;Ahmed F;Ramos R;Plikus MV;Piomelli D;Lin L;Mabou Tagne A;Squire EN;Lee HL;Fotio Y;Ramirez J;Zheng M;Torrens A;Ahmed F;Ramos R;Plikus MV;Piomelli D;Lin L;Mabou Tagne A;Squire EN;Lee HL;Fotio Y;Ramirez J;Zheng M;Torrens A;Ahmed F;Ramos R;Plikus MV;Piomelli D;
{Journal}: Pharmacology
{Volume}: 107
{Issue}: 7
{Year}: 2022
{Factor}: 3.429
{DOI}: 10.1159/000524753
{Abstract}: <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.