Overexpression of cyclooxygenase-2 in adipocytes reduces fat accumulation in inguinal white adipose tissue and hepatic steatosis in high-fat fed mice

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  • Author: Danneskiold-Samsøe, Niels Banhos

    University of Copenhagen, Denmark

  • Author: Sonne, Si Brask

    University of Copenhagen, Denmark

  • Author: Larsen, Jeppe Madura

    Research group for Food Allergy, National Food Institute, Technical University of Denmark, Kemitorvet, 2800, Kgs. Lyngby, Denmark

  • Author: Normann-Hansen, Ann

    University of Copenhagen, Denmark

  • Author: Fjære, Even

    Institute of Marine Research, Norway

  • Author: Isidor, Marie Sophie

    University of Copenhagen, Denmark

  • Author: Petersen, Sidsel Rübner

    University of Copenhagen, Denmark

  • Author: Henningsen, Jeanette

    University of Copenhagen, Denmark

  • Author: Severi, Ilenia

    Universita Politecnica delle Marche, Italy

  • Author: Sartini, Loris

    Universita Politecnica delle Marche, Italy

  • Author: Schober, Yvonne

    University Hospital of Giessen and Marburg, Germany

  • Author: Wolf, Jacqueline

    University Hospital of Giessen and Marburg, Germany

  • Author: Nockher, W Andreas

    University Hospital of Giessen and Marburg, Germany

  • Author: Wolfrum, Christian

    Swiss Federal Institute of Technology Zurich, Switzerland

  • Author: Cinti, Saverio

    Universita Politecnica delle Marche, Italy

  • Author: Sina, Christian

    University Hospital of Schleswig-Holstein, Germany

  • Author: Hansen, Jacob B.

    University of Copenhagen, Denmark

  • Author: Madsen, Lise

    University of Copenhagen, Denmark

  • Author: Brix, Susanne

    Disease Systems Immunology, Section for Protein Science and Biotherapeutics, Department of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads, 2800, Kgs. Lyngby, Denmark

  • Author: Kristiansen, Karsten

    University of Copenhagen, Denmark

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Cyclooxygenases are known as important regulators of metabolism and immune processes via conversion of C20 fatty acids into various regulatory lipid mediators, and cyclooxygenase activity has been implicated in browning of white adipose tissues. We generated transgenic (TG) C57BL/6 mice expressing the Ptgs2 gene encoding cyclooxygenase-2 (COX-2) in mature adipocytes. TG mice fed a high-fat diet displayed marginally lower weight gain with less hepatic steatosis and a slight improvement in insulin sensitivity, but no difference in glucose tolerance. Compared to littermate wildtype mice, TG mice selectively reduced inguinal white adipose tissue (iWAT) mass and fat cell size, whereas the epididymal (eWAT) fat depot remained unchanged. The changes in iWAT were accompanied by increased levels of specific COX-derived lipid mediators and increased mRNA levels of interleukin-33, interleukin-4 and arginase-1, but not increased expression of uncoupling protein 1 or increased energy expenditure. Epididymal WAT (eWAT) in TG mice exhibited few changes except from increased infiltration with eosinophils. Our findings suggest a role for COX-2-derived lipid mediators from adipocytes in mediating type 2 immunity cues in subcutaneous WAT associated with decreased hepatic steatosis, but with no accompanying induction of browning and increased energy expenditure.
Original languageEnglish
Article number8979
JournalScientific Reports
Volume9
Issue number1
Number of pages13
ISSN2045-2322
DOIs
Publication statusPublished - 2019
CitationsWeb of Science® Times Cited: No match on DOI

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