The aim of the present study was to evaluate the effects of ST (rosuvastatin) and GZ (rosiglitazone) on IR (insulin resistance) and on liver as well as adipose tissue in mice fed on an HF (high-fat) diet. Our data show that treatment with ST resulted in a marked improvement in insulin sensitivity characterized by enhanced glucose clearance during the insulin tolerance test and a 70% decrease in the HOMA-IR (homoeostasis model assessment of insulin resistance) index level (P=0.0008). The ST-treated mice exhibited lower gains in BM (body mass; −8%; P<0.01) and visceral fat pad thickness (−60%; P<0.01) compared with the untreated HF group. In comparison with HF-diet-fed mice, HF+ST-treated mice showed a significant reduction in hepatomegaly and liver steatosis (−6%, P<0.05; and −21%, P<0.01 respectively). In HF+ST-treated mice, the hepatic TAG (triacylglycerol) levels were reduced by 58% compared with the HF group (P<0.01). In addition, the expression of SREBP-1c (sterol-regulatory-element-binding protein-1c) was decreased by 50% in the livers of HF+ST-treated mice (P<0.01) relative to the HF-diet-fed mice. The levels of resistin were lower in the HF+ST-treated group compared with the HF group (44% less, P< 0.01). In conclusion, we demonstrated that ST treatment improved insulin sensitivity and decreased liver steatosis in mice fed on an HF diet. Furthermore, ST reduced BM gains, improved the circulating levels of plasma cholesterol and TAG, and reduced hepatic TAG, which was concomitant with lower resistin levels.

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