| First Author | Todoric J | Year | 2011 |
| Journal | Diabetes | Volume | 60 |
| Issue | 6 | Pages | 1668-76 |
| PubMed ID | 21536945 | Mgi Jnum | J:177949 |
| Mgi Id | MGI:5296726 | Doi | 10.2337/db10-1628 |
| Citation | Todoric J, et al. (2011) Cross-talk between interferon-gamma and hedgehog signaling regulates adipogenesis. Diabetes 60(6):1668-76 |
| abstractText | OBJECTIVE: T cells and level of the cytokine interferon-gamma (IFN-gamma) 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-gamma 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-gamma and Hh signaling. Genetic dissection using Ifngr1(-/-) and Stat1(-/-) mouse embryonic fibroblasts, and ultimately, anti-IFN-gamma 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-gamma signaling, we showed that IFN-gamma 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-gamma depletion in mice identify the system as intact in adipose tissue in vivo. CONCLUSIONS: These results identify a novel antagonistic cross-talk between IFN-gamma and Hh signaling in white adipose tissue and demonstrate IFN-gamma as a potent inhibitor of Hh signaling. |
