Adipocyte Lipolysis-stimulated Interleukin-6 Production Requires Sphingosine Kinase 1 Activity

Zhang, Wenliang; Mottillo, Emilio P.; Zhao, Jiawei; Gartung, Allison; VanHecke, Garrett C.; Lee, Jen Fu; Maddipati, Krishna Rao; Xu, Haiyan; Ahn, Young Hoon; Proia, Richard L.; Granneman, James G.; Lee, Menq Jer

doi:10.1074/jbc.m114.601096

Cited by 62 publications

(47 citation statements)

References 49 publications

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“…We previously reported that adipose ADRB3-triggered lipolysis activates stress kinases such as c-Jun N-terminal kinase (JNK) (15,16). As shown in Fig.…”

Section: Resultsmentioning

confidence: 95%

“…Previous work has shown that excessive lipolysis is associated with adipose tissue inflammation and immune cell infiltration (15,16,33). However, pro-inflammatory lipid mediators produced by adipocyte lipolysis remain to be defined.…”

Section: Discussionmentioning

confidence: 99%

“…We then determined which ISO-increased lipid mediators are regulated by the activation of HSL. Differentiated 3T3-L1 mouse adipocytes were pretreated for 1 h in the presence or absence of BAY 59-9435, a selective HSL inhibitor (15,16), followed by treatment with and without ISO for an additional 3 h (15, 16). As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…To determine whether expression of COX-2 is sufficient to induce expression of CCL2 in the absence of isoproterenol, we acutely transduced 3T3-L1-CAR cells with COX-2 expressing adenoviruses (16). As shown in Fig.…”

Section: Lipolysis-stimulated Ccl2/mcp-1 Expression Is Dependent On Jmentioning

confidence: 99%

“…COX-2 Inhibition Abrogates ADRB3-stimulated CCL2/ MCP-1 Up-regulation in Mice-Next, we injected C57BL/6 male mice with and without CL 316-243 to induce the adipose tissue lipolysis (15,16). Mice were pre-treated with or without Table 1).…”

Section: Lipolysis-stimulated Ccl2/mcp-1 Expression Is Dependent On Jmentioning

confidence: 99%

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Characterization of Eicosanoids Produced by Adipocyte Lipolysis

Gartung

Zhao

Chen

et al. 2016

Journal of Biological Chemistry

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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 ␤-adrenergic activation elevated levels of approximately fifty lipid species, including metabolites of cyclooxygenases, lipoxygenases, epoxygenases, and other sources. Moreover, we found that ␤-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/NFB signaling pathway and inhibition of the JNK/NFB 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 ␤-adrenergic activation and prevented recruitment of macrophage/monocyte to adipose tissue. Collectively, our data indicate that excessive adipocyte lipolysis activates the JNK/NFB pathway leading to the up-regulation of COX-2 expression and recruitment of inflammatory macrophages.

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“…We previously reported that adipose ADRB3-triggered lipolysis activates stress kinases such as c-Jun N-terminal kinase (JNK) (15,16). As shown in Fig.…”

Section: Resultsmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Lipolysis-stimulated Ccl2/mcp-1 Expression Is Dependent On Jmentioning

confidence: 99%

Section: Lipolysis-stimulated Ccl2/mcp-1 Expression Is Dependent On Jmentioning

confidence: 99%

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Characterization of Eicosanoids Produced by Adipocyte Lipolysis

Gartung

Zhao

Chen

et al. 2016

Journal of Biological Chemistry

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Sphingolipids in Adipose: Kin or Foe?

Valentine

Cowart

2022

Sphingolipid Metabolism and Metabolic Disease

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Geniposide augments apoptosis in fibroblast-like synoviocytes by restoring hypoxia-enhanced JNK-BNIP3-mediated autophagy

Ran,

Yan,

Yanhong

et al. 2023

Inflamm. Res.

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As the main effector cells of chronic in ammation and hyperplasia of synovium, broblast-like synoviocytes (FLSs) show abnormal proliferation and insu cient apoptosis in hypoxic microenvironment, which is due to the increase of BNIP3-mediated autophagy. This study aimed to explore the mechanism of geniposide (GE) on hypoxia-induced hyper-proliferative FLSs with a focus on autophagy and JNK-BNIP3 pathway. Materials and methodsThe dynamic changes of autophagy and apoptosis and the expression of hypoxia related proteins in adjuvant arthritis (AA) rats were detected by immunohistochemistry and Western blot. The proliferation, autophagy, apoptosis and mitochondrial state of FLSs were detected by CCK-8, ow cytometry, immuno uorescence and transmission electron microscopy, respectively. ResultsThe excessive accumulation of BNIP3 in synovium of AA rats was accompanied by inhibition of apoptosis and increase of autophagy. GE inhibited the expression of BNIP3, enhanced apoptosis and decreased autophagy, and improved chronic in ammation and hyperplasia of synovium. The amount of autophagy under different oxygen concentrations was the key to mediate the different survival rates of FLSs, and the inhibition of autophagy triggered apoptosis. GE suppresssed the proliferation of FLSs, and down-regulated autophagy, leading to the accumulation of ROS and the decrease of mitochondrial membrane potential (MMP), induced the increase of apoptosis, and suppressed the accumulation of BNIP3 and the hyperphosphorylation of JNK. ConclusionsGE inhibited autophagy by restoring the hypoxia-induced activated JNK-BNIP3 pathway, inducing mitochondrial oxidative damage, augmented apoptosis and decreased survival rate of FLSs. into the nucleus, activates the expression of BNIP3, inhibits the Bcl-2/Bcl-XL/Beclin-1 complex to release Beclin-1. BNIP3 further combined with LC3 to promote autophagy, resulting in reduced apoptosis and enhanced proliferation of FLSs.

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Adipocyte Lipolysis-stimulated Interleukin-6 Production Requires Sphingosine Kinase 1 Activity

Cited by 62 publications

References 49 publications

Characterization of Eicosanoids Produced by Adipocyte Lipolysis

Characterization of Eicosanoids Produced by Adipocyte Lipolysis

Sphingolipids in Adipose: Kin or Foe?

Geniposide augments apoptosis in fibroblast-like synoviocytes by restoring hypoxia-enhanced JNK-BNIP3-mediated autophagy

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