Cross-talk between interferon-? and hedgehog signaling regulates adipogenesis.

ABSTRACT: OBJECTIVE: T cells and level of the cytokine interferon-? (IFN-?) 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-? 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-? and Hh signaling. Genetic dissection using Ifngr1(-/-) and Stat1(-/-) mouse embryonic fibroblasts, and ultimately, anti-IFN-? 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-? signaling, we showed that IFN-? 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-? depletion in mice identify the system as intact in adipose tissue in vivo. CONCLUSIONS: These results identify a novel antagonistic cross-talk between IFN-? and Hh signaling in white adipose tissue and demonstrate IFN-? as a potent inhibitor of Hh signaling.

SUBMITTER: Todoric J 

PROVIDER: S-EPMC3114396 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature