Abstract
BackgroundLipids are known to play crucial roles in the development of life-style related risk factors such as obesity, dyslipoproteinemia, hypertension and diabetes. The first selective cannabinoid-1 receptor blocker rimonabant, an anorectic anti-obesity drug, was frequently used in conjunction with diet and exercise for patients with a body mass index greater than 30 kg/m2 with associated risk factors such as type II diabetes and dyslipidaemia in the past. Less is known about the impact of this drug on the regulation of lipid metabolism in plasma and liver in the early stage of obesity.Methodology/Principal FindingsWe designed a four-week parallel controlled intervention on apolipoprotein E3 Leiden cholesteryl ester transfer protein (ApoE*3Leiden.CETP) transgenic mice with mild overweight and hypercholesterolemia. A liquid chromatography–linear ion trap-Fourier transform ion cyclotron resonance-mass spectrometric approach was employed to investigate plasma and liver lipid responses to the rimonabant intervention. Rimonabant was found to induce a significant body weight loss (9.4%, p<0.05) and a significant plasma total cholesterol reduction (24%, p<0.05). Six plasma and three liver lipids in ApoE*3Leiden.CETP transgenic mice were detected to most significantly respond to rimonabant treatment. Distinct lipid patterns between the mice were observed for both plasma and liver samples in rimonabant treatment vs. non-treated controls. This study successfully applied, for the first time, systems biology based lipidomics approaches to evaluate treatment effects of rimonabant in the early stage of obesity.ConclusionThe effects of rimonabant on lipid metabolism and body weight reduction in the early stage obesity were shown to be moderate in ApoE*3Leiden.CETP mice on high-fat diet.
Highlights
Obesity, a major risk factor for serious diet-related chronic diseases such as diabetes and cardiovascular disease, is commonly stated as critically important compositions of the metabolic syndrome [1,2]
The effects of rimonabant on lipid metabolism and body weight reduction in the early stage obesity were shown to be moderate in ApoE*3Leiden.CETP mice on high-fat diet
In this paper we reported the results of the study of largescale lipids in plasma and liver of 16 female ApoE*3Leiden.CETP mice, 8 of which were subjected to a period of 4 weeks of rimonabant intervention and 8 untreated animals
Summary
A major risk factor for serious diet-related chronic diseases such as diabetes and cardiovascular disease, is commonly stated as critically important compositions of the metabolic syndrome [1,2]. Non-alcoholic fatty liver is observed in obese subjects with liver disease. This disease is frequently caused by complex hepatocellular metabolic dysfunctions due to the impaired insulin action, leading to disordered metabolism of fat and free fatty acids and subsequent oxidant mediated damage to the hepatocytes [6]. Lipids are known to play crucial roles in the development of life-style related risk factors such as obesity, dyslipoproteinemia, hypertension and diabetes. Less is known about the impact of this drug on the regulation of lipid metabolism in plasma and liver in the early stage of obesity
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