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C/EBPbeta knockdown prevents fatty acid induced inflammatory gene progression, macrophage infiltration and insulin resistance in vivo and in vitro
Author(s) -
Rahman Shaikh Mizanoor,
Janssen Rachel,
Houssaye B.A.,
Friedman Jed
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.871.7
Subject(s) - inflammation , adipose tissue , steatosis , gene knockdown , insulin resistance , ccaat enhancer binding proteins , biology , endocrinology , tumor necrosis factor alpha , medicine , cancer research , transcription factor , insulin , immunology , gene , biochemistry , dna binding protein
Obesity is associated with chronic, low grade inflammation, abnormal cytokine production, macrophage infiltration into adipose tissue, and insulin resistance. CCAAT/enhancer binding protein‐beta (C/EBPb) is a transcription factor that plays a key role in hepatic steatosis, inflammation, and ER stress. Here we show that global C/EBPb gene deletion prevented high fat diet (16 wks) induced increases in adipose tissue inflammatory genes TNFa, MCP1, and IL6 along with macrophage marker gene CD68. Immunohistochemistry with F4/80 revealed absent macrophage infiltration into adipose tissue of C/EBPb KO mice. Moreover, C/EBPb KO mice had increased mRNA expression of anti‐inflammatory adiponectin and superoxide dismutase (SOD) in adipose tissues. In RAW 264.7 macrophage cells and in 3T3L1 mature adipocytes, palmitate treatment robustly increased C/EBPb and inflammatory genes, while siRNA mediated knock down of C/EBPb prevented palmitate mediated induction of C/EBPb, MCP1, and IL6 and loss of insulin stimulated AKT activation and PI3‐kinase activity. These results suggest that C/EBPb plays a crucial role in dietary fat induced inflammation and insulin resistance in vivo and in vitro. Thus, C/EBPb might be an important therapeutic target for prevention of obesity induced inflammation, insulin resistance and macrophage infiltration. Funded by NIH DK059767 & DERC P&F (University of Colorado Denver).