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

Niels Banhos Danneskiold-Samsøe, Si Brask Sonne, Jeppe Madura Larsen, Ann Normann Hansen, Even Fjære, Marie Sophie Isidor, Sidsel Rübner Petersen, Jeanette Henningsen, Ilenia Severi, Loris Sartini, Yvonne Schober, Jacqueline Wolf, W Andreas Nockher, Christian Wolfrum, Saverio Cinti, Christian Sina, Jacob B Hansen, Lise Madsen, Susanne Brix*, Karsten Kristiansen

*Corresponding author for this work

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Abstract

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

Cite this

Banhos Danneskiold-Samsøe, Niels ; Sonne, Si Brask ; Larsen, Jeppe Madura ; Hansen, Ann Normann ; Fjære, Even ; Isidor, Marie Sophie ; Petersen, Sidsel Rübner ; Henningsen, Jeanette ; Severi, Ilenia ; Sartini, Loris ; Schober, Yvonne ; Wolf, Jacqueline ; Nockher, W Andreas ; Wolfrum, Christian ; Cinti, Saverio ; Sina, Christian ; Hansen, Jacob B ; Madsen, Lise ; Brix, Susanne ; Kristiansen, Karsten. / Overexpression of cyclooxygenase-2 in adipocytes reduces fat accumulation in inguinal white adipose tissue and hepatic steatosis in high-fat fed mice. In: Scientific Reports. 2019 ; Vol. 9, No. 1.
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title = "Overexpression of cyclooxygenase-2 in adipocytes reduces fat accumulation in inguinal white adipose tissue and hepatic steatosis in high-fat fed mice",
abstract = "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.",
author = "{Banhos Danneskiold-Sams{\o}e}, Niels and Sonne, {Si Brask} and Larsen, {Jeppe Madura} and Hansen, {Ann Normann} and Even Fj{\ae}re and Isidor, {Marie Sophie} and Petersen, {Sidsel R{\"u}bner} and Jeanette Henningsen and Ilenia Severi and Loris Sartini and Yvonne Schober and Jacqueline Wolf and Nockher, {W Andreas} and Christian Wolfrum and Saverio Cinti and Christian Sina and Hansen, {Jacob B} and Lise Madsen and Susanne Brix and Karsten Kristiansen",
year = "2019",
doi = "10.1038/s41598-019-45062-w",
language = "English",
volume = "9",
journal = "Scientific Reports",
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Banhos Danneskiold-Samsøe, N, Sonne, SB, Larsen, JM, Hansen, AN, Fjære, E, Isidor, MS, Petersen, SR, Henningsen, J, Severi, I, Sartini, L, Schober, Y, Wolf, J, Nockher, WA, Wolfrum, C, Cinti, S, Sina, C, Hansen, JB, Madsen, L, Brix, S & Kristiansen, K 2019, 'Overexpression of cyclooxygenase-2 in adipocytes reduces fat accumulation in inguinal white adipose tissue and hepatic steatosis in high-fat fed mice', Scientific Reports, vol. 9, no. 1, 8979. https://doi.org/10.1038/s41598-019-45062-w

Overexpression of cyclooxygenase-2 in adipocytes reduces fat accumulation in inguinal white adipose tissue and hepatic steatosis in high-fat fed mice. / Banhos Danneskiold-Samsøe, Niels; Sonne, Si Brask; Larsen, Jeppe Madura; Hansen, Ann Normann; Fjære, Even; Isidor, Marie Sophie; Petersen, Sidsel Rübner; Henningsen, Jeanette; Severi, Ilenia; Sartini, Loris; Schober, Yvonne; Wolf, Jacqueline; Nockher, W Andreas; Wolfrum, Christian; Cinti, Saverio; Sina, Christian; Hansen, Jacob B; Madsen, Lise; Brix, Susanne; Kristiansen, Karsten.

In: Scientific Reports, Vol. 9, No. 1, 8979, 2019.

Research output: Contribution to journalJournal articleResearchpeer-review

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T1 - Overexpression of cyclooxygenase-2 in adipocytes reduces fat accumulation in inguinal white adipose tissue and hepatic steatosis in high-fat fed mice

AU - Banhos Danneskiold-Samsøe, Niels

AU - Sonne, Si Brask

AU - Larsen, Jeppe Madura

AU - Hansen, Ann Normann

AU - Fjære, Even

AU - Isidor, Marie Sophie

AU - Petersen, Sidsel Rübner

AU - Henningsen, Jeanette

AU - Severi, Ilenia

AU - Sartini, Loris

AU - Schober, Yvonne

AU - Wolf, Jacqueline

AU - Nockher, W Andreas

AU - Wolfrum, Christian

AU - Cinti, Saverio

AU - Sina, Christian

AU - Hansen, Jacob B

AU - Madsen, Lise

AU - Brix, Susanne

AU - Kristiansen, Karsten

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

U2 - 10.1038/s41598-019-45062-w

DO - 10.1038/s41598-019-45062-w

M3 - Journal article

C2 - 31222118

VL - 9

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 8979

ER -