Cobalt chloride-induced hypoxia stimulates inflammatory response in adipocytes

Objective To explore the relationship between hypoxia induced by cobalt chloride( CoCl2 ) and inflammation in 3T3-LI adipocytes, and the underlying molecular mechanism. Methods 3T3-L1 pre-adipocytes were induced under standard differentiation process. Differentiated 3T3-L1 adipocytes were incubated with CoCl2 to induce hypoxia. The mRNA and protein expressions of hypoxia inducible factor-1 α ( HIF-1 α ), glucose transporter 1 ( Glut1 ), adipocytokines, and inflammatory cytokines, as well as the related signaling pathways were determined with quantitative realtime-PCR and Western-blot in this cell model. Results CoCl2 at the concentration of 200 μmol/L significantly up-regulated HIF-1 α and Glut1 expressions. After adipocytes were treated with CoCl2, the mRNA levels of endoplasmic reticulum stress marker genes, such as C/EBP homologous protein (CHOP) and glucose-regulated protein78 (GRP78) were markedly increased, adiponectin mRNA expression was significantly decreased, while resistin and leptin mRNA expressions were significantly increased. In addition, the mRNA expressions of cyclooxygenase 2, interleukin-6, and other inflammatory factors were also increased. The phosphorylation of IκBα,which could inhibit the activation of NF-κB, was stimulated by CoCl2. ConclusionsThe results indicate that hypoxia may induce inflammatory response via NF-κB activiation in adipocytes. Key words: Hypoxia;  Adipocyte;  Endoplasmic reticulumstress;  Inflammation