Control of Adipose Tissue Inflammation Through TRB1
- Anke Ostertag1,
- Allan Jones1,
- Adam J. Rose1,
- Maria Liebert1,
- Stefan Kleinsorg1,
- Anja Reimann1,
- Alexandros Vegiopoulos1,
- Mauricio Berriel Diaz1,
- Daniela Strzoda1,
- Masahiro Yamamoto2,
- Takashi Satoh2,
- Shizuo Akira2 and
- Stephan Herzig1
- 1Emmy Noether and Marie Curie Research Group, Molecular Metabolic Control, DKFZ-ZMBH Alliance, German Cancer Research Center Heidelberg, Heidelberg, Germany;
- 2Department of Host Defense, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
- Corresponding author: Stephan Herzig, .
A.J. and A.J.R. contributed equally to this article.
OBJECTIVE Based on its role as an energy storage compartment and endocrine organ, white adipose tissue (WAT) fulfills a critical function in the maintenance of whole-body energy homeostasis. Indeed, WAT dysfunction is connected to obesity-related type 2 diabetes triggered at least partly by an inflammatory response in adipocytes. The pseudokinase tribbles (TRB) 3 has been identified by us and others as a critical regulator of hepatic glucose homeostasis in type 2 diabetes and WAT lipid homeostasis. Therefore, this study aimed to test the hypothesis that the TRB gene family fulfills broader functions in the integration of metabolic and inflammatory pathways in various tissues.
RESEARCH DESIGN AND METHODS To determine the role of TRB family members for WAT function, we profiled the expression patterns of TRB13 under healthy and metabolic stress conditions. The differentially expressed TRB1 was functionally characterized in loss-of-function animal and primary adipocyte models.
RESULTS Here, we show that the expression of TRB1 was specifically upregulated during acute and chronic inflammation in WAT of mice. Deficiency of TRB1 was found to impair cytokine gene expression in white adipocytes and to protect against high-fat diet–induced obesity. In adipocytes, TRB1 served as a nuclear transcriptional coactivator for the nuclear factor κB subunit RelA, thereby promoting the induction of proinflammatory cytokines in these cells.
CONCLUSIONS As inflammation is typically seen in sepsis, insulin resistance, and obesity-related type 2 diabetes, the dual role of TRB1 as both a target and a (co) activator of inflammatory signaling might provide a molecular rationale for the amplification of proinflammatory responses in WAT in these subjects.
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- © 2010 by the American Diabetes Association.
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