EFFECTS OF BRANCHED-CHAIN AMINO ACID RESTRICTION ON INSULIN SENSITIVITY IN HIGH-FAT DIET INDUCED OBESE MICE
Objective To better understand the role and related mechanisms of BCAA in insulin resistance,we studied the effects of BCAA restriction on insulin sensitivity and islet function in high-fat diet(HFD)induced insulin resistance mouse model.Methods Male 3 months old C57BL/6J mice were randomly divided into three groups,and fed normal diet,high-fat diet and high-fat diet with 50%of BCAA restriction for 24 weeks.At the end of the experiment,the glucose tolerance test(GTT)was performed.After overnight fast,mice were killed and serum and pancreas were collected.Serum levels of BCAA,glucose and insulin were tested and HOMA-IR was calculated.The pathological changes of pancreas were observed by hematoxylin-eosin staining(HE).Insulin content in islet was detected by immunofluorescence,and the apoptosis of islet was observed by TUNEL staining.Results After 24 weeks feeding,the body weight,fasting serum levels of glucose,insulin and BCAA,insulin resistance index,and area under curve(AUC)of GTT were significantly higher than those in the control group.Compared with the HFD group,the serum BCAA level and body weight were significantly decreased in the BCAA restriction group,but there was no significant difference in fasting glucose,insulin or AUC of GTT between the two groups.Compared with the control group,some islets in the HFD group showed irregular morphology and vacuolar degeneration,and the insulin content in the islet were increased.The BCAA restriction group had relatively regular islet morphology,and the area of pancreatic islets,the number of islet,insulin content of islet and apoptosis of islet cells were decreased compared with the HFD group.Conclusion Long-term BCAA restriction combined with HFD did not have significant effects on the overall insulin sensitivity,but it exerted protective actions on pancreatic islet β cells.