Altered hepatic gene expression after activation of a Gi-coupled designer GPCR

By using DREADD technology, we found that activating Gi signaling in hepatocytes promotes hepatic glucose production. While we demonstrated that intact JNK signaling is required for maximal glucose output after stimulation of hepatic Gi signaling, other pathways may also contribute to this response. To obtain information about such non-JNK-dependent pathways, we studied changes in hepatic gene expression in an unbiased fashion using RNA-seq analysis. In this study, we used a viral delivery strategy to selectivity express a Gi-coupled DREADD (full name: hM4Di) in mouse hepatocytes (Hep-Di mice). We prepared liver RNA from Hep-Di mice 30 min after injection with either CNO (10 mg/kg i.p.) or saline (control) and then subjected these RNA samples to RNA-seq analysis.