Effects Of IL-33 On 3T3-L1 Cells And Obese Mice Models Induced By High-fat Diet

BackgroundObesity is a syndrome caused by the interaction of genetics,diet,lifestyle and environment.In recent years,obesity is on the rise worldwide,and the imbalance of immune is one of its pathogenesis.IL-33 is a new member of the IL-1 family and is classically associated with type 2-like immune responses.Some studies have reported the relationship between IL-33 and obesity in the last several years,but the results are not completely consistent,or the autoregulation of IL-33 on its distribution in various tissues has not been reported.Therefore,this study mainly discusses the effect of recombinant IL-33 on the 3T3-L1 preadipocytes and the obesity models induced by high-fat diet,observes the distribution of IL-33 among the tissues of obese mice,and provides new thoughts for understanding the pathogenesis of obesity and its associated metabolic diseases.ObjectiveAimed at investigating the effects of interleukin-33 on 3T3-L1 cells and obese mice models induced by high-fat diet.MethodsWhile 3T3-L1 preadipocytes were being induced for 10 days,different concentrations of IL-33 were added,and the effects of different concentrations of IL-33 on the lipid formation of 3T3-L1 were observed by oil red O staining.Western blot and real-time PCR were applied to detect the expression of AceCS1 and PPARγ.8-week-old C57BL/6 male mice were randomly divided into three groups: normal diet group,high fat diet group,and IL-33 treatment group.14 weeks later,detect the serum glucose and blood lipid of all mice,evaluat glucose and insulin tolerance,and analyze the changes of immune cells in spleen and adipose tissue.In order to observe the lipid infiltration,samples of liver and different adipose tissues were stained by hematoxylin and eosin(HE).ELISA was performed to measure the level of IL-33 in serum.Western blotting was used to assess the levels of IL-33,AceCS1 and PPARγ in different tissues.Expression of AceCS1 and PPARγ was detected by realtime PCR.Results1.Through inducing 3T3-L1 with various concentrations of IL-33,30ng/m IL-33 had the most significant inhibitory effect on lipid synthesis.Western blot and real-time PCR results showed that 30ng/mL IL-33 could reduce the levels of AceCS1 and PPARγ(P<0.05).2.Exogenous of IL-33 reduced the weight of epididymal and perirenal adipose tissue of obese mice induced by high-fat diet(P<0.05).HE staining results indicated that IL-33 reduced lipid infiltration in liver tissue of obese mice.3.The high-fat diet resulted in not only weight gain in mice(P<0.05),but also the increased level of IL-33 in the serum of mice(P<0.05).In this case,the increased IL-33 in the serum of mice was reversed by the exogenous of IL-33 treatment(P<0.05).4.Compared with normal diet group,IL-33 shows high expression in subcutaneous adipose tissue of obese mice induced by high-fat diet,and is down-regulated in epididymal adipose tissue,perirenal adipose tissue,liver,skeletal muscle and brown adipose tissue(P<0.05).Surprisingly,IL-33 treatment reversed the above trend to varying degrees.5.IL-33 resulted in decreased levels of AceCS1 and PPARγ in subcutaneous and epididymal adipose tissue of obese mice induced by high-fat diet(P<0.05).6.IL-33 reduced fasting blood glucose(P<0.05),increased serum total cholesterol(P<0.05),and decreased the area under the curve of glucose and insulin tolerance in obese mice induced by high-fat diet(P<0.05).7.IL-33 improved type 1 inflammation in adipose tissue and systemic circulation of obese mice induced by a high-fat diet(P<0.05).Conclusion1.IL-33 reduces lipid synthesis and metabolism in 3T3-L1 preadipocytes.2.In obese mice induced by high-fat diet,IL-33 regulates its own distribution in different tissues,which makes it more inclined to normal diet group.3.IL-33 alleviates inflammation and dyslipidemia in obese mice models induced by high-fat diet,reduces liver fat infiltration,and improves glucose and insulin tolerance.