Faculty Collaboration Database

Characterization of Eicosanoids Produced by Adipocyte Lipolysis: IMPLICATION OF CYCLOOXYGENASE-2 IN ADIPOSE INFLAMMATION. J Biol Chem 2016 Jul 29;291(31):16001-10

Date

06/02/2016

Pubmed ID

27246851

Pubmed Central ID

PMC4965551

DOI

10.1074/jbc.M116.725937

Scopus ID

2-s2.0-84979737354 (requires institutional sign-in at Scopus site)   47 Citations

Abstract

Excessive adipocyte lipolysis generates lipid mediators and triggers inflammation in adipose tissue. However, the specific roles of lipolysis-generated mediators in adipose inflammation remain to be elucidated. In the present study, cultured 3T3-L1 adipocytes were treated with isoproterenol to activate lipolysis and the fatty acyl lipidome of released lipids was determined by using LC-MS/MS. We observed that β-adrenergic activation elevated levels of approximately fifty lipid species, including metabolites of cyclooxygenases, lipoxygenases, epoxygenases, and other sources. Moreover, we found that β-adrenergic activation induced cyclooxygenase 2 (COX-2), not COX-1, expression in a manner that depended on activation of hormone-sensitive lipase (HSL) in cultured adipocytes and in the epididymal white adipose tissue (EWAT) of C57BL/6 mice. We found that lipolysis activates the JNK/NFκB signaling pathway and inhibition of the JNK/NFκB axis abrogated the lipolysis-stimulated COX-2 expression. In addition, pharmacological inhibition of COX-2 activity diminished levels of COX-2 metabolites during lipolytic activation. Inhibition of COX-2 abrogated the induction of CCL2/MCP-1 expression by β-adrenergic activation and prevented recruitment of macrophage/monocyte to adipose tissue. Collectively, our data indicate that excessive adipocyte lipolysis activates the JNK/NFκB pathway leading to the up-regulation of COX-2 expression and recruitment of inflammatory macrophages.

Author List

Gartung A, Zhao J, Chen S, Mottillo E, VanHecke GC, Ahn YH, Maddipati KR, Sorokin A, Granneman J, Lee MJ

Author

Andrey Sorokin PhD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

3T3-L1 Cells
Adipocytes
Animals
Chemokine CCL2
Cyclooxygenase 2
Eicosanoids
Inflammation
Lipolysis
MAP Kinase Kinase 4
Macrophages
Mice
NF-kappa B
Panniculitis
Signal Transduction
Sterol Esterase