الفهرس 
IntroductionOnly 14 pages are availabe for public view
Abstract
The present study evaluated the effect of synbiotic supplementation and/or caloric restriction given to high fat diet fed rats in the last 6 weeks of the whole study period (12 weeks). Also, study tried to show effect of return to normal diet pattern in last 6 weeks. The study evaluated different metabolic aspects including anthropometric measures, liver enzymes, lipid profile, glycemic & oxidative states and on gastrointestinal barrier integrity. Also, the study elucidated the interaction between gastrointestinal hormones as serotonin & glucagon like peptide-1, gut microbiota and its products as cecal short chain fatty acids with the obesity.
This study was carried out on 60 male adult albino rats, allocated into 6 groups:
group I: Control group (C): Rats fed with control diet for 12 weeks.
group II: High fat diet fed group (HFD): Rats fed with high fat diet for 12 weeks.
group III: High fat diet shifted to control diet group (HFD-CD): Rats fed with high fat diet for 6 weeks then shifted to control diet for another 6 weeks.
group IV: Synbiotic-supplemented high fat diet fed group (S-HFD): Rats fed with high fat diet for 6 weeks then supplemented with synbiotic while being fed with high fat diet for another 6 weeks.
group V: Caloric restriction-treated high fat diet fed group (CR-HFD): Rats fed with high fat diet for 6 weeks then put on a caloric restriction regimen while being fed with high fat diet for another 6 weeks.
group VI: Combined synbiotic & caloric restriction treated group (S-CR-HFD): Rats fed with high fat diet for 6 weeks then put on a caloric restriction regimen and synbiotic supplementation while being fed with high fat diet for the next 6 weeks.
All rats were subjected weekly to determination of body weight (BW), body mass index (BMI), Lee index and waist circumference (WC).
On the day of sacrifice, the overnight fasted rats were weighed and anaesthetized by intraperitoneal (i.p) injection of thiopental sodium, in a dose of 40 mg/kg B.W. The final body weight, naso-anal length (needed to calculate the BMI and the Lee index), waist circumferences were measured for all rats. And the blood was collected from the aorta for later determination of the following:
• Lipid profile: Serum triglycerides, total cholesterol, high density lipoprotein (HDL) and calculation of low density lipoprotein (LDL) levels & atherogenic index.
• Liver enzymes: Serum transaminases (AST and ALT).
• Insulin resistance assessment: Fasting blood sugar, fasting serum insulin and HOMA-IR calculation.
• Gut hormones: Serum serotonin and serum glucagon like peptide 1 (GLP-1).
• Oxidant/antioxidant markers: Serum malondialdehyde (MDA), serum glutathione peroxidases level.
• Intestinal barrier marker: Serum zonulin.
After blood collection, the cecal content were collected into clean storage labeled aliquots contain 150 µl EDTA solution (its concentration was 0.29 gm in 100 ml distilled water) for assessment of quantitative cecal short chain fatty acids.
The liver and the intestinal segment were isolated and rapidly immersed in 10% formalin solution for histological examination.
The encountered results showed that high fat diet fed group (HFD), has a significant increase in the anthropometric measures (final body weight, body weight gain %, body mass index, body mass index gain %, lee index and lee index gain %). Also, metabolic parameters, liver transaminases (AST &ALT), Fasting blood glucose, serum insulin, HOMA-IR, serum triglyceride, LDL-c, MDA and zonulin were significantly increased, while serum HDL-c, GPx, serotonin, GLP-1 and cecal quantitative SCFAs was significantly decreased.
In both groups of caloric restriction regimen and synbiotic supplementation, there were marked significant decrease in anthropometric measures (body weight, body weight gain %, body mass index, body mass index gain %, lee index and lee index gain %) and marked improvement of the metabolic parameters, as it significantly decreased the liver transaminases (AST & ALT), fasting blood glucose, serum insulin, HOMA-IR, serum triglyceride, LDL-c, while HDL-c, GPx, serotonin, GLP-1 and cecal quantitative SCFAs was significantly increased.
Comparing the caloric restricted group and synbiotic group, the caloric restricted group improved the anthropometric measures than synbiotic group. But, the synbiotic group improved the metabolic parameters (lipid profile, glycemic state, oxidative stress status, serum serotonin, GLP-1, zonulin and cecal SCFAs) than caloric restricted group. There was no significant difference in liver enzymes level in both groups.
The combined caloric restriction and synbiotic supplemented group showed more improve in liver enzymes, lipid profile, glycemic state, oxidative stress status, serum GLP-1, zonulin, cecal SCFAs than each group separately. Also, it improved anthropometric measures more than synbiotic group and serum serotonin compared to caloric restricted group. So, combination of both regimens give better results in loss weight and improve metabolic status than each separate group.
Regarding, the switching of diet from high fat diet to control diet, it caused significant improvement of most anthropometric and metabolic parameters (liver enzymes, lipid profile, insulin resistance, oxidative markers, serum serotonin, SCFAs and intestinal gut barrier), while serum GLP-1 was not changed.
Comparing shift to control diet with caloric restriction group, they were similar regarding improvement of metabolic parameters (liver enzymes, lipid profile, glycemic state, oxidative stress and GLP-1) but, caloric restriction produces more significant improvement regarding anthropometric measures, serum serotonin, cecal SCFAs and intestinal barrier permeability marker (zonulin). This could be explained by the shorter duration of recovery and it may be in need for more time for better results.
Comparing shift to control diet with synbiotic supplemented group, synbiotic exhibited apart significant improvement in all metabolic parameters (liver enzymes, lipid profile, glycemic state, oxidative stress, GLP-1, serotonin, zonulin and cecal SCFAs) except being equal in anthropometric measurements. This could be related to absence of fibers (prebiotic) which was present in synbiotic causing defect in SCFAs production which have important roles in improvement of most metabolic parameters and intestinal barrier integrity.
Conclusion:
• Caloric restriction regimen (6 weeks) can improve anthropometric measurements more than metabolic parameters.
• Synbiotic supplementation (6 weeks) can improve metabolic parameters more than anthropometric measurements.
• Both caloric restriction and synbiotic supplemented groups can ameliorate the high fat diet induced dyslipidemia, insulin resistance, oxidative stress states, dysbiosis and gut barrier disruption. Those effects mediated through enhancement of serum serotonin, GLP-1 and cecal SCFAs.
• Combination of both regimens in one group enhances and potentiates the beneficial effect of each other.
• Switching of diet from high fat diet to control diet can improve most of anthropometric and metabolic parameters. But the effect of caloric restriction on HFD induced changes was more clear than shifting to standard diet.