Obesity-Related Upregulation of Monocyte Chemotactic Factors in Adipocytes

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Obesity-Related Upregulation of Monocyte Chemotactic Factors in Adipocytes

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dc.contributor.author Jiao, Ping
dc.contributor.author Chen, Qiu
dc.contributor.author Shah, Suketu
dc.contributor.author Du, Jing
dc.contributor.author Tao, Bo
dc.contributor.author Yan, Weiqun
dc.contributor.author Xu, Haiyan
dc.contributor.author Tzameli, Iphigenia
dc.date.accessioned 2011-11-22T16:10:39Z
dc.date.issued 2009
dc.identifier.citation Jiao, Ping, Qiu Chen, Suketu Shah, Jing Du, Bo Tao, Iphigenia Tzameli, Weiqun Yan, and Haiyan Xu. 2009. Obesity-Related Upregulation of Monocyte Chemotactic Factors in Adipocytes. Diabetes 58(1): 104-115. en_US
dc.identifier.issn 0012-1797 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:5350700
dc.description.abstract OBJECTIVE—We sought to evaluate the entire picture of all monocyte chemotactic factors that potentially contribute to adipose tissue macrophage accumulation in obesity. RESEARCH DESIGN AND METHODS—Expression and regulation of members in the entire chemokine superfamily were evaluated in adipose tissue and isolated adipocytes of obese versus lean mice. Kinetics of adipose tissue macrophage infiltration was characterized by fluorescence-activated cell sorting. The effects of fatty acids on stimulation of chemokine expression in adipocytes and underlying mechanisms were investigated. RESULTS—Six monocyte chemotactic factors were found to be predominantly upregulated in isolated adipocytes versus stromal vascular cells in obese mice for the first time, although most of them were previously reported to be upregulated in whole adipose tissue. In diet-induced obese mice, adipose tissue enlargement, increase of adipocyte number, and elevation of multiple chemokine expression precede the initiation of macrophage infiltration. Free fatty acids (FFAs) are found to be inducers for upregulating these chemokines in 3T3-L1 adipocytes, and this effect can be partially blunted by reducing Toll-like receptor 4 expression. FFAs induce expression of monocyte chemotactic factors in adipocytes via both transcription-dependent and -independent mechanisms. In contrast to the reported role of JNK as the exclusive mediator of FFA-induced monocyte chemoattractant protein-1 (MCP-1) expression in macrophages, we show a novel role of inhibitor of κB kinase-β (IKKβ) in mediating FFA-induced upregulation of all six chemokines and a role of JNK in FFA-induced upregulation of MCP-1 and MCP-3. CONCLUSIONS—Multiple chemokines derived from adipocytes might contribute to obesity-related WAT macrophage infiltration with FFAs as potential triggers and involvement of both IKKβ and JNK pathways. en_US
dc.language.iso en_US en_US
dc.publisher American Diabetes Association en_US
dc.relation.isversionof doi:10.2337/db07-1344 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2606857/pdf/ en_US
dash.license LAA
dc.title Obesity-Related Upregulation of Monocyte Chemotactic Factors in Adipocytes en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal Diabetes en_US
dash.depositing.author Tzameli, Iphigenia
dc.date.available 2011-11-22T16:10:39Z
dash.affiliation.other HMS^Clinical and Translational Science Center en_US

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