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Regulation of IL‐12 expression in adipocytes during inflammatory stress
Author(s) -
Nam Heesun,
Ferguson Bradley S,
Stephens Jacqueline M,
Morrison Ron F
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.910.13
Subject(s) - adipocyte , inflammation , tumor necrosis factor alpha , adipose tissue , adipokine , insulin resistance , biology , endocrinology , interleukin 6 , gene expression , microbiology and biotechnology , medicine , cytokine , gene , immunology , insulin , genetics
Chronic inflammation is an important element of pathogenic mechanisms linking obesity and diabetes. During development of insulin resistance, adipose tissue accumulates macrophages and secretes a plethora of inflammatory adipokines that regulate lipid metabolism and systemic insulin resistance. Interleukin‐12 (IL‐12) is a heterodimeric pro‐inflammatory cytokine encoded by independent IL‐12α and IL‐12β genes. While IL‐12 serum levels are known to be elevated in type 2 diabetics, cellular origin has yet to be determined. Using 3T3‐L1 adipocytes stimulated with tumor necrosis factor α (TNFα) as a model of inflammatory stress, we show with qRT‐PCR that both IL‐12 genes were equivocally expressed in undifferentiated preadipocytes relative to mature adipocytes suggesting that expression is a function of inflammatory status rather than adipocyte differentiation. Following TNFαstimulation, each IL‐12 gene was dramatically and acutely induced with overlapping kinetics supporting the synthesis of a functionally mature p70 heterodimer. Using inhibitors for specific signaling pathways, we also show differential regulation of inducible gene expression where NFkB and ERK signaling was predominant in IL‐12α and IL‐12β expression, respectively. These findings indicate that diverse mechanisms mediate IL‐12 gene expression in adipocytes during inflammatory stress. Supported by NIH (5R21DK072067‐02).