Ursolic Acid Ameliorates Insulin Resistance Of Adipose Tissue In Ageing Rats

Objective: Ageing often results in insulin resistance(IR)and chronic inflammation,and adipose is one of the tissues in which inflammation and IR occur earliest during this process.The present study investigated the effect and underlying mechanisms of ursolic acid(UA)on adipose IR and inflammation in ageing rats.Methods:Twenty-five specific pathogen-free male Sprague-Dawley rats with hyperglycemia and hyperlipidemia were randomly divided into three groups: the untreated ageing group(aged;n=9),the groups supplemented with either low-UA 10 mg/kg(UA-L;n=8)or high-UA 50mg/kg(UA-H)(UA-H;n=8);Take another eight young rats as normal control group: gavage with 5% gum arabic(young;n=8).All rats were intragastrically administered once daily via oral gavage for 7 weeks.On the6 th weekend of the experiment,overnight fasting blood was collected and plasma was prepared to measure biochemical indicators;western blotting was employed to analyze of the expression of insulin signaling proteins and inflammatory factors in the epididymis white adipose tissue(eWAT).Results: The results revealed that treatment with UA-H decreased eWAT weight,the ratio of eWAT weight/body weight,fasted insulin and triglyceride,HOMA-IR and Adipo-IR index in ageing rats,indicating the amelioration of systemic and adipose tissue IR.Mechanistically,UA-H administration upregulated the phosphorylated protein kinase B,the ratio of p-Akt to protein kinase B(Akt),and total and cellular membrane glucose transporter 4(GLUT4)protein levels in eWAT of ageing rats.Conversely,UA inhibited the increase in nuclear factor-κB expression and proinflammatory cytokines interleukin(IL)6 and(IL)1β.Conclusions: The current results indicate that UA may ameliorate adipose IR,which is associated with activation of the Akt-GLUT4 signaling pathway and inhibition of inflammation in ageing rats.