Effect of Leucine Intervention on Bile Acid Metabolism in Insulin Resistant Rats / 华中科技大学学报(医学版)

ABSTRACT

Objective@#To observe the effects of leucine on insulin resistance，serum bile acid levels，and expression of genes related to bile acid metabolism，and to reveal the mechanism of leucine intervention on glucose and lipid metabolism in insulin resistant rats. @*Methods@#Twenty-four male Sprague-Dawley rats aged 6 weeks were randomly divided into three groups and fed on normal diet，high fat diet，and high fat diet supplemented with 1.5% leucine respectively. At the end of 32 weeks，glucose tolerance test（GTT）and insulin tolerance test（ITT）were performed，and the area under the curve of glucose（AUC）was calculated.Then the rats were sacrificed，the serum and tissues samples were collected.Serum insulin and glucose levels were measured，insulin resistance index（HOMA-IR）calculated，and insulin sensitivity evaluated.The levels of total cholesterol（TC）and triglycerides（TG）in the serum and liver were detected.The expressions of bile acid synthesis related genes liver X recepter（LXRα），farnesoid X receptor（FXR），cholesterol 7α-hydroxylase（CYP7A1）and cholesterol 27-hydroxylase（CYP27A1）mRNA in the liver were determined by real-time reverse transcription PCR（RT-PCR），and the levels of 17 bile acids in the serum by ultra-high performance liquid chromatography tandem mass spectrometry（UPLC-MS/MS）. @*Results@#Leucine intervention were determined significantly reduced serum TC，TG and liver TG levels and improved lipid metabolism in rats on high fat diet. Leucine had no significant effect on glucose and insulin levels，but could effectively reduce the HOMA-IR and AUC of glucose tolerance test and decrease insulin resistance. Leucine significantly increased serum bile acid levels and LXRα，FXR，CYP27A1 mRNA levels but had no effect on CYP7A1 mRNA expression @*Conclusion@#Leucine intervention significantly increased bile acid synthesis in insulin resistant rats，thereby reducing the accumulation of serum lipids，improving glucose and lipid metabolism and insulin sensitivity.