The anti-adipogenic effect of macrophage-conditioned medium requires the IKKβ/NF-κB pathway.
Macrophage-secreted factors inhibit adipogenesis, but the underlying mechanism is not well understood. Our objective was to determine if anti-adipogenic signaling pathways in human preadipocytes are activated by macrophage-conditioned medium (MacCM). Human abdominal subcutaneous stromal preadipocytes were treated with adipogenic inducers in either standard medium or medium conditioned by human THP-1 macrophages. THP-1-MacCM increased inhibitor of κB kinase β (IKKβ) phosphorylation, inhibitor of NF-κB α (IκBα) degradation, and NF-κB activity in human preadipocytes in a time-dependent manner. Concomitant treatment of human abdominal subcutaneous preadipocytes with sc-514, a selective inhibitor of IKKβ, prevented the inhibitory effect of THP-1-MacCM on lipid accumulation and expression of adipogenic markers. Our data indicate that activation of the preadipocyte IKKβ/NF-κB pathway is required for the anti-adipogenic effect of THP-1-MacCM on human adipogenesis.
Yarmo
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MN
Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Gagnon
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Sorisky
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D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D050156:Adipogenesis / Q000187:drug effects; D000328:Adult; D002460:Cell Line; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008875:Middle Aged; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects
D017077:Culture Media, Conditioned; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D000072000:NF-KappaB Inhibitor alpha; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse