The Role Of Autophagy In Ectopic Lipid Deposition In Pancreas And Insulin Resistance

Obeject: Establish a high-fat-diet induced obese rat model, while giving theautophagy inhibitor, testing the degree of pancreas fat deposition and autophagyrelated protein beclin1expression levels, analysis the relationship betweenautophagy activity and the degree of fat deposition in pancreas.Methods:24SD male rats were fed after1week adaptively, who were randomlydivided into3groups. Group A: Fed with normal-diet, Group B: Fed with high-fatdiet, Group C: Fed with high fat diet and chloroquine, each group had8cases. Afterfeeding8weeks, Take the pancreatic tissue and paraffin sections were stained withHE, observe and calculate the degree of the pancreas fat deposition. Detect the levelof triglycerides, total cholesterol and fast insulin levels. And calculate the degree ofinsulin resistance. Detect the autophagy related protion beclin1expression levels.Results:1Comparing the growth characters in three groupsBody weight of rats in three groups was no significant difference in the entry. After2,4,6,8weeks of feeding, compared with group A, body weight, Lee’s index in groupB,and body weight, abdominal circumference in group C were significantlyincreased(p<0.05); After2,4weeks of feeding, compared with group B, abdominalcircumference and Lees index in group C were significantly increased(p<0.05); There were no significant difference in body weight, abdominal circumference, Lees indexand stem length in group B and group C.2changes of biochemical indicators2.1Comparing the levels of glucose metabosim characters in three groups.Compared with the group A, glucose tolerance test indicates the levels of0,20,40,60,120min blood glucose, Glucose area under the curve, FINS and HOMA-IR in group Band C were significantly increased(p<0.05). Compared with the group B, the bloodglucose of20min,40min and AUCGwere significantly increased in group C(p<0.05).2.2Comparing the levels of TG and TC in three groupsCompared with group A, TG and TC levels were significantly increased in group B andC(p<0.05). Compared with group B, TG and TC levels were significantly(p<0.05).3The results of HE stainWe observed a large number of lipid droplets deposition in pancreas tissue of group Cin HE stain. In group B, there are many small lipid droplets deposition in the pancreastissue. There is no significant lipid droplets deposition in the pancreas tissue of group A.Using image analysis software, calculated (intralobular and interlobular) the percentageof fat cells in each high power field. Compared with the group A and group B, thedegree of pancreas fat deposition were significantly increased in group C(p<0.05).4Comparing the levels of the weight of pancreas and abdominal fat in threegroupsCompared with the group A, the weight of pancreas and abdominal fat weight weresignificantly increased in group B and C(p<0.05). There is no significantly difference inpancreas and abdominal fat weight in group B and C.5Correlation AnalysisThe analysis of the associativity of the degree of fat deposition in pancreas with lipidsand insulin resistance. The degree of fat deposition in pancreas correlated positivelywith body weight, abdominal circumference, Lee’s index, FPG, TG, TC, FINS, HOMA-IR, AUCG, pancreas and abdominal fat weight. In a multiple regression analysis,TG, Lee’s index, pancreas fat and FINS were independently associated with thepancreas fat deposition.6The expression of Beclin1in three groupsIn normal diet droup, Beclin1protin have a quantitive expression. Comparing thenormal diet group, the expression of Beclin1was significantly increased in group B andsignificantly decreased in group C(P<0.05).Conclusion:1. Long term high-fat diet, lipid droplets can deposition in pancreas in SD rats.2. Losing the protective effect of autophagy, impaired glucose tolerance, blood lipidsand pancreatic fat deposition were further aggravated.3. Linear correlation analysis showed that TG, Lee’s index, the weight of pancreatictissue and FINS were independent risk factors in pancreas fat deposition in obesitySD rats4. High fat diet can activity the expression level of autophagy related protein Beclin1.The SD rat pancreas fat deposition were further aggravated when the activity ofautophagy was inhibited.