Figure 1.

CAR suppresses gluconeogenic gene expression through inhibiting PGC1α activity. A, Cotransfection of CAR inhibited the PGC1α-responsive activation of the G6Pase luciferase reporter gene in 293T cells. B, Mouse primary hepatocytes isolated from WT (left panel) or CAR null (right panel) mice were treated with TCPOBOP (TC) (500nM) or DMSO for 12 hours before treatment of FSK (10μM) for 2 hours. The gene expression was measured by real-time PCR. C, Human primary hepatocytes were treated with 6-(4-Chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime (1μM) for 12 hours, followed by a FSK (10μM) treatment for 2 hours. The gene expression was measured by real-time PCR. D, Primary hepatocyte from WT mice infected with Ad-scramble RNAi or Ad-PGC1α RNAi for 48 hours was treated with TC (500nM) or DMSO for 12 hours before treatment of FSK (10μM) for 2 hours. The gene expression was measured by real-time PCR. E, Mouse primary hepatocytes were pretreated with TC (500nM) overnight in the maintenance medium. Glucose production was measured after incubation with FSK (10μM) with or without TC (500nM) in the glucose-free medium for 4 hours. F and G, Primary hepatocytes from CAR null mice were infected with Ad-GFP, Ad-CAR, or Ad-PGC1α and treated with or without TC (500nM) for 12 hours before measuring the mRNA expression of G6Pase and Pepck (F) and glucose production (G). H, Hepatic expression of G6Pase and Pepck in fed, overnight fasted (16 h), and refed (12 h) WT and CAR null mice. n = 5 for each group. I, Expression of CAR and PGC1α in mouse liver during the fasting-refed transition (left panel, n = 4 for each group) and upon a 12-week HFD feeding (right panel, n = 5 for each group). *, P < .05; **, P < .01.