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Pleiotropic effects of rosuvastatin on the glucose metabolism and the subcutaneous and visceral adipose tissue behavior in C57Bl/6 mice.

Neto-Ferreira R, Rocha VN, Souza-Mello V, Mandarim-de-Lacerda CA, de Carvalho JJ - Diabetol Metab Syndr (2013)

Bottom Line: The rosuvastatin treatment decreased the adiposity and the adipocyte size in the HF-R10 and HF-R20 groups.This redistribution improved the fasting glucose and the glucose intolerance.Rosuvastatin also improved the liver morphology and ultrastructure in a dose-dependent manner.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Ultrastructure and Tecidual Biology, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, 20551-030, Rio de Janeiro, RJ, Brazil. jjcarv@gmail.com.

ABSTRACT
The aim of this study was to evaluate whether rosuvastatin (HMG-CoA reductase inhibitor) modulates the carbohydrate and lipid metabolism, the development of non-alcoholic fatty liver disease (NAFLD), and the increase in body mass in a model of diet-induced obesity. Male C57Bl/6 mice (3-months-old) were fed a high-fat diet (HF, 60% lipids) or the standard chow (SC, 10% lipids) for 15 weeks. The animals were then treated with 10 mg/kg/day (HF-R10 group), 20 mg/kg/day (HF-R20), or 40 mg/kg/day (HF-R40) of rosuvastatin for five weeks. The HF diet led to glucose intolerance, insulin resistance, weight gain, increased visceral adiposity with adipocyte hypertrophy, and hepatic steatosis (micro and macrovesicular). The rosuvastatin treatment decreased the adiposity and the adipocyte size in the HF-R10 and HF-R20 groups. In addition, rosuvastatin changed the pattern of fat distribution in the HF-R40 group because more fat was stored subcutaneously than in visceral depots. This redistribution improved the fasting glucose and the glucose intolerance. Rosuvastatin also improved the liver morphology and ultrastructure in a dose-dependent manner. In conclusion, rosuvastatin exerts pleiotropic effects through a dose-dependent improvement of glucose intolerance, insulin sensitivity and NAFLD and changes the fat distribution from visceral to subcutaneous fat depots in a mouse model of diet-induced obesity.

No MeSH data available.


Related in: MedlinePlus

Liver photomicrographs stained with hematoxylin and eosin (bar = 30 μm). Note the normal liver morphology in the SC group, whereas the HF groups exhibit micro and macrovesicular steatosis. The rosuvastatin treatment ameliorated the steatosis in a dose-dependent manner, as observed in the treated groups: HF-R10, HF-R20 and HF-R40. The arrows indicate the steatosis. The symbols indicate a difference compared with [a] the SC group, [b] the HF group and [c] the HF-R10 group.
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Figure 3: Liver photomicrographs stained with hematoxylin and eosin (bar = 30 μm). Note the normal liver morphology in the SC group, whereas the HF groups exhibit micro and macrovesicular steatosis. The rosuvastatin treatment ameliorated the steatosis in a dose-dependent manner, as observed in the treated groups: HF-R10, HF-R20 and HF-R40. The arrows indicate the steatosis. The symbols indicate a difference compared with [a] the SC group, [b] the HF group and [c] the HF-R10 group.

Mentions: Excessive fat intake led to liver enlargement in all of the groups that received the HF diet compared with the SC group (Figure 2A). The levels of hepatic triglycerides were significantly higher in the HF group (+400%, p = 0.0001) than in the SC group (Figure 2B). The rosuvastatin treatment dose-dependently decreased the hepatic triglycerides in the mice from the HF-R10, HF-R20 and HF-R40 groups compared with the untreated HF group (p <0.0001, Figure 2B). As observed through light microscopy, liver steatosis was recurrent in our study, especially in the HF group, which showed severe microvesicular and macrovesicular steatosis (Figure 3). Although both the HF-R20 and HF-R40 groups showed an attenuation of the hepatic steatosis, only the HF-R40 group was statistically different from the untreated HF group. The electron microscopy also revealed hepatocytes with abundant lipid vesicles in the HF group (Figure 4), which characterizes the existence of macro and microvesicular steatosis and a complete breakdown of the cytoarchitecture. Smaller and scarcer mitochondria were also found. The mitochondrial cristae were difficult to observe, and a remarkable breakdown of the rough endoplasmic reticulum and Golgi apparatus was found (Figure 4). In contrast, the treated groups showed smaller and less frequent fat droplets, which confirms the findings obtained through light microscopy. The untreated HF mice exhibited a lower density of mitochondria compared with the SC (p <0.001), HF-R20 (p <0.001) and HF-R40 (p <0.05) groups (Figure 4).


Pleiotropic effects of rosuvastatin on the glucose metabolism and the subcutaneous and visceral adipose tissue behavior in C57Bl/6 mice.

Neto-Ferreira R, Rocha VN, Souza-Mello V, Mandarim-de-Lacerda CA, de Carvalho JJ - Diabetol Metab Syndr (2013)

Liver photomicrographs stained with hematoxylin and eosin (bar = 30 μm). Note the normal liver morphology in the SC group, whereas the HF groups exhibit micro and macrovesicular steatosis. The rosuvastatin treatment ameliorated the steatosis in a dose-dependent manner, as observed in the treated groups: HF-R10, HF-R20 and HF-R40. The arrows indicate the steatosis. The symbols indicate a difference compared with [a] the SC group, [b] the HF group and [c] the HF-R10 group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3716873&req=5

Figure 3: Liver photomicrographs stained with hematoxylin and eosin (bar = 30 μm). Note the normal liver morphology in the SC group, whereas the HF groups exhibit micro and macrovesicular steatosis. The rosuvastatin treatment ameliorated the steatosis in a dose-dependent manner, as observed in the treated groups: HF-R10, HF-R20 and HF-R40. The arrows indicate the steatosis. The symbols indicate a difference compared with [a] the SC group, [b] the HF group and [c] the HF-R10 group.
Mentions: Excessive fat intake led to liver enlargement in all of the groups that received the HF diet compared with the SC group (Figure 2A). The levels of hepatic triglycerides were significantly higher in the HF group (+400%, p = 0.0001) than in the SC group (Figure 2B). The rosuvastatin treatment dose-dependently decreased the hepatic triglycerides in the mice from the HF-R10, HF-R20 and HF-R40 groups compared with the untreated HF group (p <0.0001, Figure 2B). As observed through light microscopy, liver steatosis was recurrent in our study, especially in the HF group, which showed severe microvesicular and macrovesicular steatosis (Figure 3). Although both the HF-R20 and HF-R40 groups showed an attenuation of the hepatic steatosis, only the HF-R40 group was statistically different from the untreated HF group. The electron microscopy also revealed hepatocytes with abundant lipid vesicles in the HF group (Figure 4), which characterizes the existence of macro and microvesicular steatosis and a complete breakdown of the cytoarchitecture. Smaller and scarcer mitochondria were also found. The mitochondrial cristae were difficult to observe, and a remarkable breakdown of the rough endoplasmic reticulum and Golgi apparatus was found (Figure 4). In contrast, the treated groups showed smaller and less frequent fat droplets, which confirms the findings obtained through light microscopy. The untreated HF mice exhibited a lower density of mitochondria compared with the SC (p <0.001), HF-R20 (p <0.001) and HF-R40 (p <0.05) groups (Figure 4).

Bottom Line: The rosuvastatin treatment decreased the adiposity and the adipocyte size in the HF-R10 and HF-R20 groups.This redistribution improved the fasting glucose and the glucose intolerance.Rosuvastatin also improved the liver morphology and ultrastructure in a dose-dependent manner.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Ultrastructure and Tecidual Biology, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, 20551-030, Rio de Janeiro, RJ, Brazil. jjcarv@gmail.com.

ABSTRACT
The aim of this study was to evaluate whether rosuvastatin (HMG-CoA reductase inhibitor) modulates the carbohydrate and lipid metabolism, the development of non-alcoholic fatty liver disease (NAFLD), and the increase in body mass in a model of diet-induced obesity. Male C57Bl/6 mice (3-months-old) were fed a high-fat diet (HF, 60% lipids) or the standard chow (SC, 10% lipids) for 15 weeks. The animals were then treated with 10 mg/kg/day (HF-R10 group), 20 mg/kg/day (HF-R20), or 40 mg/kg/day (HF-R40) of rosuvastatin for five weeks. The HF diet led to glucose intolerance, insulin resistance, weight gain, increased visceral adiposity with adipocyte hypertrophy, and hepatic steatosis (micro and macrovesicular). The rosuvastatin treatment decreased the adiposity and the adipocyte size in the HF-R10 and HF-R20 groups. In addition, rosuvastatin changed the pattern of fat distribution in the HF-R40 group because more fat was stored subcutaneously than in visceral depots. This redistribution improved the fasting glucose and the glucose intolerance. Rosuvastatin also improved the liver morphology and ultrastructure in a dose-dependent manner. In conclusion, rosuvastatin exerts pleiotropic effects through a dose-dependent improvement of glucose intolerance, insulin sensitivity and NAFLD and changes the fat distribution from visceral to subcutaneous fat depots in a mouse model of diet-induced obesity.

No MeSH data available.


Related in: MedlinePlus