Lin L.a· Mabou Tagne A.a· Squire E.N.a· Lee H.-L.a· Fotio Y.a· Ramirez J.a· Zheng M.a· Torrens A.a· Ahmed F.a· Ramos R.b,c· Plikus M.V.b,c· Piomelli D.a,d,e

Author affiliations

aDepartment of Anatomy and Neurobiology, University of California, Irvine, CA, USA
bDepartment of Developmental and Cell Biology, University of California, Irvine, CA, USA
cNSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, CA, USA
dDepartment of Biological Chemistry University of California, Irvine, CA, USA
eDepartment of Pharmaceutical Sciences, University of California Irvine, Irvine, CA, USA

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Article / Publication Details

First-Page Preview

Received: December 06, 2021
Accepted: April 01, 2022
Published online: June 10, 2022

Number of Print Pages: 10
Number of Figures: 3
Number of Tables: 1

ISSN: 0031-7012 (Print)
eISSN: 1423-0313 (Online)

For additional information: https://www.karger.com/PHA

Abstract

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.

© 2022 S. Karger AG, Basel

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First-Page Preview

Received: December 06, 2021
Accepted: April 01, 2022
Published online: June 10, 2022

Number of Print Pages: 10
Number of Figures: 3
Number of Tables: 1

ISSN: 0031-7012 (Print)
eISSN: 1423-0313 (Online)

For additional information: https://www.karger.com/PHA

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