Μελέτη φλεγμονοδών παραγόντων στο σπλαγχνικό λίπος και στο περιφερικό αίμα σε επίμυες με μεταβολικό σύνδρομο

Abstract

Background and Aim: Obesity is the epidemic of the 21st century. The Metabolic Syndrome (MetS) is directly associated with obesity. The MetS is a combination of metabolic abnormalities including abdominal obesity, glucose intolerance, hypertension and dyslipidemia. The prevalence of MetS is increasing owing to lifestyle changes leading to obesity. The MetS is associated with an increased risk of cardiovascular events; thus, the implementation of optimal conservative and/or pharmacological measures is essential. Besides lifestyle modification modalities (including diet and exercise for weight reduction), drug treatment should aim to normalize blood pressure, total cholesterol, low–density lipoprotein–cholesterol (LDL–C), high–density lipoprotein–cholesterol (HDL–C), triglyceride and glucose values. Treatment of atherogenic dyslipidemia should be a major goal since it is associated with an increased risk of cardiovascular disease (CVD). The treatment–of– choice for the optimal management of the dyslipidemia of the MetS is not clearly defined. Thus, we compared the efficacy of 4 drug regimes for the management of this dyslipidemia in a mouse model. Materials and Methods: A total of 60 C57Bl6 mice comprised the study group. The first 10 received standard mouse food for the whole experiment (control group). The remaining 50 mice received atherogenic diet for 14 weeks until the development of the MetS. The mice were then divided into 5 groups: the 1st group continued receiving atherogenic diet, while the other 4 groups received atherogenic diet plus ezetimibe (10 mg/kg/day), fenofibrate (100 mg/kg/day), low– (10 mg/kg/day) or high–dose (40 mg/kg/day) atorvastatin, respectively, for another 8 weeks. Results: The mice receiving atherogenic diet developed the MetS. Their mean weight increased significantly (Mean body weight: from 28.3 ± 1.4 g to 40.3 ± 3.3 g; p<0.0001). Similar significant fluctuations were observed in the lipidemic profile: Mean fasting blood glucose: from 145 ± 22 mg/dl to 212 ± 37 mg/dl; p<0.0001; mean fasting total cholesterol: from 92 ± 10 mg/dl to 148 ± 19 mg/dl; p<0.0001; mean fasting LDL–C: from 43.6 ± 9.1 mg/dl to 108.0 ± 16.8 mg/dl; p<0.0001. High–dose atorvastatin treatment achieved the best lipid profile compared with low– dose atorvastatin, ezetimibe and fibrate therapy. The lipid profile of mice receiving atherogenic diet plus high–dose atorvastatin treatment was similar with mice on regular chow. Conclusions: High–dose atorvastatin treatment resulted in optimization of the lipid profile in the presence of a high–fat atherogenic diet in a mouse model. Our results suggest that high–dose atorvastatin treatment may be the optimal treatment option for the dyslipidemia associated with MetS. Nevertheless, verification of these results in humans is required before any definite conclusions can be drawn.