Does rosuvastatin cause weight gain
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Does Rosuvastatin Cause Weight Gain?
Introduction to Rosuvastatin and Weight Gain Concerns
Rosuvastatin, a widely used statin, is primarily prescribed to manage cholesterol levels and reduce cardiovascular risk. However, concerns about potential side effects, including weight gain, have been raised. This article synthesizes findings from multiple studies to determine whether rosuvastatin contributes to weight gain.
Rosuvastatin and Body Weight in Animal Models
Effects on Mice with Diet-Induced Obesity
Research involving male C57Bl/6 mice fed a high-fat diet (HFD) demonstrated that rosuvastatin treatment did not lead to weight gain. Instead, it decreased adiposity and adipocyte size, particularly at doses of 10 mg/kg/day and 20 mg/kg/day. Additionally, rosuvastatin altered fat distribution, favoring subcutaneous over visceral fat storage, which improved glucose intolerance and insulin sensitivity.
Comparative Study in Female Rats
A study comparing the effects of simvastatin, rosuvastatin, and fenofibrate on female rats treated with oral contraceptives and a high-fat diet found that rosuvastatin did not prevent weight gain. However, it effectively inhibited significant rises in triglycerides and total cholesterol levels, unlike simvastatin. This suggests that while rosuvastatin may not directly influence weight, it positively impacts lipid profiles.
Mechanisms and Pharmacokinetics
Hepatic Uptake and Blood Concentration
In rats with high-fat diet-induced obesity, rosuvastatin's blood concentration increased due to decreased hepatic uptake, mediated by the inhibition of the hepatic pregnane X receptor (Pxr)-organic anion transporting polypeptide 2 (Oatp2) pathway. This pharmacokinetic alteration suggests that obesity can affect rosuvastatin metabolism, potentially leading to higher blood levels and associated muscle toxicity risks.
Dose-Dependent Metabolic Effects
Further studies on diet-induced obesity in mice revealed that higher doses of rosuvastatin (40 mg/kg) significantly improved glucometabolic profiles, including fasting blood glucose and insulin sensitivity, compared to lower doses (20 mg/kg). These findings indicate that rosuvastatin may ameliorate metabolic disturbances without causing weight gain.
Rosuvastatin and Blood Pressure in Obese Mice
In obese dyslipidaemic mice, rosuvastatin normalized blood pressure and its variability without affecting body weight. This effect was linked to the upregulation of PPARgamma and SOD1 in the endothelium, suggesting a unique vasculoprotective role of rosuvastatin independent of weight changes.
Conclusion
Current research indicates that rosuvastatin does not cause weight gain. Instead, it may offer beneficial effects on fat distribution, lipid profiles, and metabolic parameters in animal models. While these findings are promising, further studies in human subjects are necessary to confirm these effects and fully understand the implications of rosuvastatin therapy on body weight.
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