Journal article
Adipocyte lipolysis-stimulated interleukin-6 production requires sphingosine kinase 1 activity
The Journal of biological chemistry, v 289(46), pp 32178-32185
14 Nov 2014
PMID: 25253697
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Adipocyte lipolysis can increase the production of inflammatory cytokines such as interleukin-6 (IL-6) that promote insulin resistance. However, the mechanisms that link lipolysis with inflammation remain elusive. Acute activation of β3-adrenergic receptors (ADRB3) triggers lipolysis and up-regulates production of IL-6 in adipocytes, and both of these effects are blocked by pharmacological inhibition of hormone-sensitive lipase. We report that stimulation of ADRB3 induces expression of sphingosine kinase 1 (SphK1) and increases sphingosine 1-phosphate production in adipocytes in a manner that also depends on hormone-sensitive lipase activity. Mechanistically, we found that adipose lipolysis-induced SphK1 up-regulation is mediated by the c-Jun N-terminal kinase (JNK)/activating protein-1 signaling pathway. Inhibition of SphK1 by sphingosine kinase inhibitor 2 diminished the ADRB3-induced IL-6 production both in vitro and in vivo. Induction of IL-6 by ADRB3 activation was suppressed by siRNA knockdown of Sphk1 in cultured adipocytes and was severely attenuated in Sphk1 null mice. Conversely, ectopic expression of SphK1 increased IL-6 expression in adipocytes. Collectively, these data demonstrate that SphK1 is a critical mediator in lipolysis-triggered inflammation in adipocytes.
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Details
- Title
- Adipocyte lipolysis-stimulated interleukin-6 production requires sphingosine kinase 1 activity
- Creators
- Wenliang Zhang - Wayne State UniversityEmilio P Mottillo - Wayne State UniversityJiawei Zhao - Wayne State UniversityAllison Gartung - Wayne State UniversityGarrett C VanHecke - Wayne State UniversityJen-Fu LeeKrishna R Maddipati - Wayne State UniversityHaiyan Xu - Brown UniversityYoung-Hoon Ahn - Wayne State UniversityRichard L Proia - National Institutes of HealthJames G Granneman - Wayne State UniversityMenq-Jer Lee - Wayne State University
- Publication Details
- The Journal of biological chemistry, v 289(46), pp 32178-32185
- Publisher
- ASBMB Publications / Elsevier
- Grant note
- Canadian Institutes of Health Research R01 DK076629 / NIDDK NIH HHS P30 DK020572 / NIDDK NIH HHS Intramural NIH HHS P60 DK020572 / NIDDK NIH HHS HL-071071 / NHLBI NIH HHS R01 DK062292 / NIDDK NIH HHS 5P600-DK020572 / NIDDK NIH HHS R56 DK062292 / NIDDK NIH HHS R01 HL071071 / NHLBI NIH HHS DK-062292 / NIDDK NIH HHS DK-076229 / NIDDK NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Arts and Sciences; Chemistry; Drexel University
- Web of Science ID
- WOS:000345314700045
- Scopus ID
- 2-s2.0-84911164049
- Other Identifier
- 991020100192604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology