We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Cross-Talk Between Interferon-γ and Hedgehog Signaling Regulates Adipogenesis.
- Authors
Todoric, Jelena; Strobl, Birgit; Jais, Alexander; Boucheron, Nicole; Bayer, Martina; Amann, Sabine; Lindroos, Josefine; Teperino, Raffaele; Prager, Gerhard; Bilban, Martin; Ellmeier, Wilfried; Krempler, Franz; Müller, Mathias; Wagner, Oswald; Patsch, Wolfgang; Pospisilik, J. Andrew; Esterbauer, Harald
- Abstract
OBJECTIVE--T cells and level of the cytokine interferon-γ (IFN-γ) are increased in adipose tissue in obesity. Hedgehog (Hh) signaling has been shown to potently inhibit white adipocyte differentiation. In light of recent findings in neurons that IFN-γ/ and Hh signaling cross-talk, we examined their potential interaction in the context of adipogenesis. RESEARCH DESIGN AND METHODS--We used Hh reporter cells, cell fines, and primary adipocyte differentiation models to explore costimulation of IFN-γ/and Hh signaling. Genetic dissection using Ifngr1-/- and Stat1-/- mouse embryonic fibroblasts, and ultimately, anti-IFN-γ/neutralization and expression profiling in obese mice and humans, respectively, were used to place the findings into the in vivo context. RESULTS--T-cell supernatants directly inhibited hedgehog signaling in reporter and 3T3-L1 cells. Intriguingly, using blocking antibodies, Ifngr1-/- and Stat1-/- cells, and simultaneous activation of Hh and IFN-γ signaling, we showed that IFN-γ/directly suppresses Hh stimulation, thus rescuing adipogenesis. We confirmed our findings using primary mouse and primary human (pre)adipocytes. Importantly, robust opposing signals for Hh and T-cell pathways in obese human adipose expression profiles and IFN-γ/depletion in mice identify the system as intact in adipose tissue in vivo. CONCLUSIONS--These results identify a novel antagonistic cross-talk between IFN-γ and Hh signaling in white adipose tissue and demonstrate IFN-γ/ as a potent inhibitor of Hh signaling.
- Subjects
ADIPOSE tissues; OBESITY; CYTOKINES; INTERFERONS; GENETICS
- Publication
Diabetes, 2011, Vol 60, Issue 6, p1668
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db10-1628