期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 291, 期 31, 页码 16001-16010出版社
ELSEVIER
DOI: 10.1074/jbc.M116.725937
关键词
-
资金
- Department of Defense Grant [W81XWH-14-1-0346]
- Wayne State University
- National Institutes of Health [DK-076229, DK-062292, CA-182114]
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 beta-adrenergic activation elevated levels of approximately fifty lipid species, including metabolites of cyclooxygenases, lipoxygenases, epoxygenases, and other sources. Moreover, we found that beta-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/NF kappa B signaling pathway and inhibition of the JNK/NF kappa B 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 beta-adrenergic activation and prevented recruitment of macrophage/monocyte to adipose tissue. Collectively, our data indicate that excessive adipocyte lipolysis activates the JNK/NF-kappa B pathway leading to the up-regulation of COX-2 expression and recruitment of inflammatory macrophages.
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