Effects Of Dietary Fats On The Pancreatic Beta Cell Function And Its Possible Underlying Mechanism

Objective: We aim to investigate the effects of dietary fat on the function and endoplasmic reticulum stress of pancreatic beta cells by performing the intravenous glucose tolerance test (IVGTT) and detecting the changes in expression of p-PERK [PKR (double stranded RNA-dependent protein kinase)-like endoplasmic reticulum kinase], p-eIF2α(α-subunit of eukaryotic translational initiation factor 2) and CHOP [C/EBP (CCAAT ? enhancer-binding protein) homologous protein] in pancreatic cells.Methods: Forty male Wistar rats (250~300g) were randomly divided into four groups: a control group and three groups fed with different high fat diet. The control group (N, n=10) was fed with a regular low fatty acids diet containing 10.3% fat, 24.2% protein, and 65.5% carbohydrate as percentage of total calories. Three high fat diet groups include high monounsaturated fatty acids diet group (M, n=10), high polyunsaturated fatty acids diet group (P, n=10) and high saturated fatty acids diet group (S, n=10), which contain 35.4% fat, 17.4% protein and 47.2% carbohydrate as a percentage of total calories. The fatty acids component of M group, P group and S group were from tea oil, soybean oil and lard oil respectively. At the end of 8-weeks feeding, the body weight of each individual rat was recorded, intravenous glucose tolerance test (IVGTT) was performed and acute insulin response (AIR) [AIR=(Ins1'+Ins3'+Ins5'+Ins8')/4–FINS (fasting insulin)] was calculated. Blood samples were collected and the serum were then separated for the determination of blood lipids. Pancreas was collected for detecting p-eIF2αand p-PERK by immunohistochemisty and for p-eIF2αand CHOP by western-blot.Results: 1. After 8 weeks of diet intervention, the body weight in all high fat groups increased, but there were no statistical differences among the four groups (P >0.05). 2. At the end of 8-weeks feeding, fasting blood glucose(FBG), FINS, serum total cholesterol(TC), triglyceride(TG) and free fatty acids (FFA) of S group increased significantly compared with N group (P <0.05). The FBG and FINS of P group were significantly higher than those of N group (P <0.05). 3. BG at every time point after glucose bolus was higher than that of N group. BG at 1 min and 5 min of S group increased significantly compared with N group (P <0.01), The BG at other time points showed no significant difference from N group. There was no significant difference in BG among M group, P group and N group. INS concentration at all time points of S group decreased significantly compared with N group (P <0.05). INS concentration at 1min, 3 min and 5 min in P group and at 5min in M group after glucose bolus were statistically lower than those in N group (P <0.05). There was no statistical difference among the others. The AIRs of three high fat groups were significantly lower than that in N group. 4. Immunohistochemisty analysis showed that the expression of p-PERK and p-eIF2αin S group (P <0.01) and P group (P <0.05) increased significantly than that of N group, but there was no difference between M group and N group (P >0.05). 5. Western blot analysis showed that the protein expression of p-eIF2αand CHOP of all high fat groups increased. Among the three groups, protein levels of p-eIF2αof S group and P group were significantly higher than that of N group (P =0.014, P =0.022 respectively), and so was CHOP (P =0.007, P =0.046 respectively). However, there was no significant difference between M group and N group (P >0.05). 6. AIR was negatively correlated with p-PERK, p-eIF2αand CHOP protein expression, FBG and FINS (r=-0.890 P <0.01; r=-0.656 P <0.01; r=-0.772 P <0.01; r=-0.606 P <0.05; r=-0.865 P <0.01, respectively). CHOP protein expression was highly positively correlated with the protein levels of p-PERK, p-eIF2α(r=0.771 P <0.01; r=0.587 P <0.05, respectively). And the protein levels of p-eIF2αwas in high positive correlation with p-PERK (r=0.771 P <0.01).Conclusions: 1. The total cholesterol, triglyceride, FFAs, FBG and FINS of high fat groups increased whileβcell function decreased compared with N group. Intravenous glucose tolerance test demonstrated impaired function ofβcells in three high fat groups, of which the high saturated fatty acids diet group displayed most severe impairment. 2. High fat diets induce higher expression of p-PERK, p-eIF2αand downstream component apoptosis factor CHOP compared with normal diet. Among the three high fat diets, high saturated fatty acids diet has the most potent effect on the change of ER stress markers, and polyunsaturated fatty acids and monounsaturated fatty acids in turns. 3. High fat diets appear to impairβcell function by inducing ER stress and apoptosis.