| First Author | Rahman SM | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 41 | Pages | 34349-60 |
| PubMed ID | 22902781 | Mgi Jnum | J:191771 |
| Mgi Id | MGI:5462527 | Doi | 10.1074/jbc.M112.410613 |
| Citation | Rahman SM, et al. (2012) CCAAT/enhancer-binding protein beta (C/EBPbeta) expression regulates dietary-induced inflammation in macrophages and adipose tissue in mice. J Biol Chem 287(41):34349-60 |
| abstractText | Strong evidence exists for a link between chronic low level inflammation and dietary-induced insulin resistance; however, little is known about the transcriptional networks involved. Here we show that high fat diet (HFD) or saturated fatty acid exposure directly activates CCAAT/enhancer-binding protein beta (C/EBPbeta) protein expression in liver, adipocytes, and macrophages. Global C/EBPbeta deletion prevented HFD-induced inflammation and surprisingly increased mitochondrial gene expression in white adipose tissue along with brown adipose tissue markers PRDM16, CIDEa, and UCP1, consistent with a resistance to HFD-induced obesity. In isolated peritoneal macrophages from C/EBPbeta(-/-) mice, the anti-inflammatory gene LXRalpha and its targets SCD1 and DGAT2 were strikingly up-regulated along with IL-10, while NLRP3, a gene important for activating the inflammasome, was suppressed in response to palmitate. Using RAW 264.7 macrophage cells or 3T3-L1 adipocytes, C/EBPbeta knockdown prevented palmitate-induced inflammation and p65-NFkappaB DNA binding activity, while C/EBPbeta overexpression induced NFkappaB binding, JNK activation, and pro-inflammatory cytokine gene expression directly. Finally, chimeric bone marrow mice transplanted with bone marrow lacking C/EBPbeta(-/-) demonstrated reduced systemic and adipose tissue inflammatory markers, macrophage content, and maintained insulin sensitivity on HFD. Taken together, these results demonstrate that HFD or palmitate exposure triggers C/EBPbeta expression that controls expression of distinct aspects of alternative macrophage activation. Reducing C/EBPbeta in macrophages confers protection from HFD-induced systemic inflammation and insulin resistance, suggesting it may be an attractive therapeutic target for ameliorating obesity-induced inflammatory responses. |
