Systems analysis of hepatic insulin resistance identifies RGS4 as a key mediator of metabolic adaptation. Mus musculus

We profiled the transcriptomes of chow diet-fed and high-fat diet-fed mice across insulin stimulation time points. We also profiled the effects of metformin treatment on mouse liver transcritomes. Our temporal analyses of chow-diet and 16 week high-fat diet transcriptomics following insulin stimulation uncovered several regulator of G-protein signaling genes, particularly Rgs4, that are specifically regulated transcriptionally in HFD livers following insulin stimulation. We validated these findings with additional assays of RGS4 mRNA and protein levels and characterized this molecule's role in regulating hepatic insulin responses in mice. Overall design: Liver mRNA was profiled by sequencing from chow diet and 6 week and 16 week high-fat diet mouse livers. We sampled time points following insulin stimulation as well as following treatment with metformin. At least three mice per group/time point were used for statistical analyses.