FIG 8.

Thiocholesterol exhibits a superior activity in reducing fasting blood glucose level and improving overall glucose homeostasis in HFD-fed mice. Six-week-old WT C56BL/6 male mice were fed a high-fat diet (HFD) for 12 weeks followed by i.p. injections of vehicle (DMSO), TC (25 mg/kg), or CS (25 mg/kg) 3 times per week for 2 weeks while the mice remained on HFD. (A) Fasting blood glucose levels 24 h or 48 h after the last dose of drugs. Mice were fasted for 6 h before the blood glucose tests. (B and C) Hepatic expression of gluconeogenic genes (B) and lipogenic genes (C) 3 days after the last dose of drugs was measured by real-time PCR. The expression of each gene was arbitrarily set as 1 in mice treated with DMSO. (D and E) Shown on the right of each panel are the quantifications of GTT (D) and ITT (E) presented as areas under the curve (AUC). (F and G) Oil red O staining of the liver sections (F) and serum triglyceride and cholesterol levels (G). (H and I) Hepatic expression levels of the Sirt1 (H) and Acss (I) proteins was measured by Western blotting. Shown on the right are the densitometric quantifications of the Western blotting. Results are expressed as means ± SD from three independent experiments (5 mice per group). *, P < 0.05; **, P < 0.01; ***, P < 0.001.