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Abstract The present study was carried out in Medical Physiology Department, Faculty of Medicine, Menoufia University, Egypt. The experimental procedures, animal handling, sampling and sacrification were performed according to The International Ethical guidelines for Investigations of Laboratory Animals and the Guide for The Care and Use of Laboratory Animals. Thirty-two male Wistar albino rats, aged 20-22 weeks and weighing 250-400 gm, were acclimatized to the environmental conditions for one week, and had free access to water all through the experiment. Rats were randomly divided into four equal groups (n=8): 1. Control (C) group, in which normal rats were fed with a standard chow diet formed of 24% protein, 58% CHO, 18% fat (Hyatt et al., 2016) for 8 weeks. 2. Ketogenic diet (KD) group, in which rats were fed with KD, formed of 20% protein, 4% carbohydrate and 76% fat (Hernandez et al., 2018) for 8 weeks. This diet was designed to induce nutritional ketosis. 3. Caloric restriction (CR) group, in which rats were fed with standard rat chow, but with 40% CR, for 8 weeks (Merry, 2004). To achieve 40% CR, food intake of the freely eating control rats was measured every other day for four weeks, and then rats were given food equal to 60% of the average amount of food eaten by the freely eating control rats. 4. Intermittent fasting (IF) group, in which rats were fed with standard chow, but they were exposed to reduced meal frequency by fasting every other day (Mattson & Wan, 2005). At the end of the dietary manipulation period (after 8 week-duration), rats of all groups underwent measurement of: body weight reduction value and percentage, ALT, AST, serum albumin, serum creatinine, blood urea, lipid profile, oxidative stress markers, citrate synthase activity, ATP, HOMA-IR, FFA, BHB, open field examination test, and immune Summery 179 histopathological study of LC3 and Beclin 1. Our data show that significant body weight reduction (g) was found in KD and IF groups, when compared with C and CR groups (p value <0.001 for all). C and CR groups showed no body weight reduction. Also, a significant decrease in visceral fat of KD groups, when compared with corresponding values of C and CR groups (p value <0.001 & 0.004, respectively) was observed. Visceral fat of IF group was significantly decreased, when compared with that of C and CR groups (both p value <0.001). HOMA index showed significant increase in CR and IF groups compared to C group (P value =0.006 & 0.041, respectively) and KD group (both P value <0.001). The HOMA index in KD group was significantly decreased, when compared with that of C group (P value =0.010). The FFA of KD, CR and IF groups showed a significant increase, when compared with the corresponding value of C group. FFA in the IF and CR groups showed a significant decrease, when compared with that of KD group. FFA in IF group significantly decreased, when compared with CR group (P value <0.001 for all). Liver citrate synthase of KD, CR and IF groups was significantly increased, when compared with that of C group (p value <0.001, 0.002, <0.001, respectively). CR and IF groups showed a significant decrease of liver citrate synthase, when compared with that of KD group (p value <0.001 & 0.007, respectively). Heart citrate synthase of KD, CR and IF groups was significantly increased, when compared with that of C group (p value <0.001, <0.001 & 0.001, respectively). CR and IF groups showed a significant decrease of heart citrate synthase, when compared with that of KD group (p value 0.001 & <0.001, respectively). Summery 180 Brain citrate synthase of KD, CR and IF was significantly increased, when compared with that of C group. CR and IF groups showed a significant decrease of brain citrate synthase, when compared with that of KD group (p value <0.001 for all). HDL-C levels of KD and CR groups were significantly decreased, when compared with that of C group (P value < 0.001 & 0.033, respectively). HDL-C levels of CR and IF groups were significantly higher than that of KD group (P value 0.024 & 0.001, respectively). LDL-C levels of IF and CR groups were significantly higher than that of KD group (P value < 0.001 for all). LDL-C level of KD group was significantly increased, when compared with that of C group (P value < 0.001). Total cholesterol (TC) levels of IF and CR groups were significantly less than that of KD group (P value < 0.001 for all). TC level of KD group was significantly increased, when compared with that of C group (P value < 0.001). Triglycerides (TGs) levels of IF and CR groups were significantly lower than that of KD group (P value =0.003 & 0.001, respectively). LDLC level of KD group was significantly increased, when compared with that of C group (P value =0.020). Systolic blood pressure (SBP) of KD, CR and IF groups was significantly decreased, when compared with that of C group (P value < 0.001, 0.004 & 0.007, respectively). SBP of CR group was significantly more than those of KD and IF groups (P value =0.01 & 0.048, respectively). Total number of crossed squares in KD and IF groups was significantly increased, when compared with that of C group (P value =0.014 & 0.008, respectively). Frequency of grooming in CR and IF groups was significantly decreased, when compared with those of C group (P value =0.022 & 0.008, respectively) and KD group (p value =0.003 & 0.001, respectively). Summery 181 Frequency of rearing in CR group was significantly increased, when compared with that of C group (P value 0.043). Negative expression of beclin1 and LC3 of heart tissue samples were observed in all the four studied groups. |