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.
Keywords: NF-kappa B (NF-κB); adipocyte; adrenergic receptor; cyclooxygenase (COX); eicosanoid; inflammation; lipolysis; prostaglandin.
© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.