Comparison And Mechanism Of Obesity Models Established In Different Strains Of Mice&Antiobesity Effects And Mechanism Of LRTG

ObjectiveThe present study was designed to establish and compare different strains and gender of mouse obesity models and investigate the mechanism of development to better support the usages of mice on researches of antiobesity drugs.Furthermore, the aim of this study was to evaluate the antiobesity effect of LRTG. And to explore the mechanisms of its antiobesity effect by determining the mRNA expressions of the enzymes, proteins and receptors that involved in lipid metabolism.MethodsThe different gender mice from three different mouse strain C57BL/6J、ICR and KM were randomly assigned to two groups:a control group and a model respectively. Mice in the control groups were fed control diets, while mice in the model groups were fed high-fat diets. The body weight, fat weight, Lee’s index, morphology observation and cross-sectional area of adipocytes were determined after modeling4and8weeks, and the serum lipids levels and LPL activity were also determined by enzymatic methods. The relative expressions of hepatic PPARa and adipose PPARy, DGAT, HSL, ATGL and TGH mRNA were measured by real-time polymerase chain reaction.Male C57BL/6J mice were assigned randomly to groups of normal control, obesity model, positive control (Orlisata0.12g/kg) and high (1.2mg/kg), middle (0.6g/kg), low (0.3g/kg) doses of LRTG respectively. Animals of the normal control groups were fed with the normal diets. The rest were fed with the high-fat diets. Four weeks later, the body weight, fat weight, Lee’s index and serum lipids levels of control and model groups were detected to evaluate the success of modelling or not. And the groups treated were intragastrically administrated with drugs according to the prescribed dosage respectively for five weeks. The antiobesity effect of LRTG was evaluated through detecting the body weight, fat weight, Lee’s index, morphology observation and cross-sectional area of adipocytes and serum lipids levels. Real-time polymerase chain reaction was used to quantity relative genes expressions.ResultsIn comparison with control group, the body weight, fat weight, Lee’s index and cross-sectional area of adipocytes in C57BL/6J mice significantly increased after fed with high-fat diet for four weeks. However, the obesity indexes of ICR and KM mice changed less than C57BL/6J mice. After diet-induced for eight weeks, the obesity indexes remain at a high level, these illustrated that the C57BL/6J mice could form a good obesity model. The mechanism research shows that mRNA levels of both hepatic PPARa and adipose PPARy were increased in C57BL/6J mice fed with high-fat diet, to promote the LPL activity increased, which led to a decomposition of the serum TG. Simultaneously, the expression of adipose DGAT mRNA were up-regulated, to promote the resynthesis of TG. Adipose HSL, ATGL and TGH mRNA expressions were down-regulated, to inhibit the lipolysis, those led to a fat accumulation of adipose tissue. The alternation of these enzymes and receptors were the critical factors for obesity formation.After administrating for five weeks, orlistat and three dose groups of LRTG could all obviously reduce body weight, fat weight, Lee’s index, cross-sectional area of adipocytes and serum TC. The mechanism research shows that adipose Lep mRNA expression was up-regulated, to down-regulate the expression of adipose DGAT mRNAs, those led to an inhibition of fat synthesis. Cholesterol metabolism-related genes of HMG-CoA reductase, CYP7A1, and FXR were detected to screen the lipid-lowering target, the results showed that the hepatic CYP7A1mRNA expression were up-regulated, to promote TC transforming into bile acids and excreting it backout of the body, which led to improving cholesterol metabolism disorders caused by obesity.ConclusionC57BL/6J mice fed high-fat diet can form a good obesity model. LPL, PPARa, PPARy, DGAT, HSL, ATGL and TGH are the main mechanisms of obesity formation, and also the biomarkers of antiobesity drugs targets.LRTG has specialty of antiobesity effects that it can reduce the body weight, fat weight, Lee’s index and cross-sectional area of adipocytes significantly. And its antiobesity targets might be DGAT and Lep. In addition, LRTG has specialty of hypolipidemic effect that it can reduce serum TC concentrations significantly. And its hypolipidemic targets might be CYP7A1.