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Journal Article

Cross-Talk Between Interferon-γ and Hedgehog Signaling Regulates Adipogenesis

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Jais,  Alexander
Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Teperino,  Raffaele
Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Pospisilik,  J. Andrew
Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Citation

Todoric, J., Strobl, B., Jais, A., Boucheron, N., Bayer, M., Amann, S., et al. (2011). Cross-Talk Between Interferon-γ and Hedgehog Signaling Regulates Adipogenesis. Diabetes, 60, 1668-1676.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002B-8E2F-0
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 lines, 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.