Figure 5.

In obese mice, OCA-mediated beneficial effects on glucose metabolism were largely abolished by overexpression of miR-802. A–H: Mice were fed HF/HF diet for 7 weeks and infected with adenovirus expressing miR-802, antisense RNA for miR-802, or control virus, and OCA or Veh was administrated daily by oral gavage for 2 weeks. A: Experimental scheme. B: Levels of hepatic miR-802. C: GTT and AUC (right). D: ITT and AUC (right). E: Blood glucose levels. F: Plasma insulin levels. G: HOMA-IR index. H: Levels of the mRNAs for the indicated genes involved in glucose metabolism. I: PMHs were infected with Ad-miR802, Ad-antisense–miR-802, or control virus for 24 h and then, PA (300 μmol/L) and OCA (10 μmol/L) were added. After 24 h, glucose production was measured as described in research design and methods. J: Dietary obese mice that had been infected with adenovirus and administered OCA as described (Fig. 5A) and were treated with Veh or insulin (0.25 units/kg) for 10 min before sacrifice. Levels of the indicated proteins in liver and muscle extracts in two mice measured by immunoblotting. B–I: The mean and SD are plotted. Statistical significance was determined by one-way ANOVA, SD (n = 5). *P < 0.05, **P < 0.01. Ad, adenovirus; AUC, area under the curve; GTT, glucose tolerance test; HF/HF, high fat/high fructose; IR, insulin resistance; ITT, insulin tolerance test; ND, normal diet; PA, palmitic acid; Rel, relative; sac, sacrifice; Veh, vehicle.