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.