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. Author manuscript; available in PMC: 2017 Apr 1.
Published in final edited form as: Hepatology. 2016 Jan 16;63(4):1071–1073. doi: 10.1002/hep.28381

Figure 1. Activation of hedgehog signaling in hepatocytes promotes NAFLD development.

Figure 1

Sonic hedgehog (Shh) binds to Ptch1, which abolishes the inhibitory effect of Smoothened (Smo) on hedgehog signaling, resulting in activation of hedgehog signaling and transcription factor Gli. In NAFLD, ballooned hepatocyte-derived Shh stimulates hedgehog signaling in hepatocytes, which produce osteopontin to induce liver macrophage accumulation and NAFLD development. Hedgehog signaling is also activated in hepatic stellate cells, macrophages, and adipose tissues, which promotes NAFLD development and insulin resistance. Blocking hedgehog signaling systemically by the administration of Smo inhibitors suppress the progression of NAFLD and insulin resistance.