| Part 1:Systematic evaluation and meta-analysis of the effects of intermittent fasting on insulin resistance and oxidative stress in obese patients Objective: To systematically review the efficacy and safety of intermittent fasting on improving insulin resistance(IR)and oxidative stress markers.Methods: We electronically searched databases including PubMed,MEDLINE,EMbase,CNKI,VIP,WanFang Data,and CBM from inception to October 2018,to collect randomized controlled trials(RCT)and not randomized controlled trials(NRCT)preparations for obese patients.Two reviewers independently screened literature,extracted data,and assessed the risk of bias of included studies.Then meta-analysis was performed using stata 12.0.Results: A total of 7 RCTs and 5 NRCTS involving 518 patients were included.The quality assessment of 7 randomized controlled trials showed that the quality of studies was relatively high and the risk of bias was low.According to MINORS ’entry for assessment of non-randomized controlled experiments,the case-control experiments or cross-sectional studies are most middle-level quality.The results of meta-analysis showed that FBG in the groups treatment with intermittent fasting was superior to the control group [SMD=0.082,95%CI(-0.05,0.33),p = 0.86];There was no significant difference in FBG of obese patients after intervention compared with before intervention [SMD=0.41,95%CI(0.08,0.79),p = 0.09].The FINS of intermittent fasting group was superior to levels of that of control group [SMD=1.200,95%CI(0.99,1.42),p < 0.01],and no statistically differences of FINS after the intermittent fasting of obese patients in non-RCTS[SMD= 0.400,95%CI(0.05,0.74),p = 0.63].Compared with the control group,The HOMA-IR of intermittent fasting was significantly reduced [SMD= 0.442,95%CI(0.20,0.64),p < 0.01],the meta analysis of HOMA-IR in non-RCTS showed that there was no statistically differences after the intervention [SMD= 0.601,95%CI(0.185,1.017),p = 0.40],and the oxidative stress markers were discripted.As for the safety,only 1 RCT discriminated the adverse reactions.Symptoms of adverse reactions included hugerness,dizziness.Conclusion: Current evidence shows treatment with intermmittent fasting could improve insulin sensitivity and reduce insulin secretion in obese patients.Due to limited quality and quantity of the included studies,the above conclusion need to be verified by more high quality studies.Part 2: The effect of intermittent fasting on insulin resistance and oxidative stress in obese C57BL/6J mice Aim: To investigate the effects of intermittent fasting on insulin resistance and oxidative stress products MDA,SOD and 8-OHdG in obese mice induced by high fat.Methods: Fifty male C57BL/6J mice were fed with normal diet as control group and 40 mice were fed with high-fat diet.After 8 weeks of intervention,20 obese mice were randomly divided into obesity group(DIO)and intermittent fasting intervention group(DIO+IF).At this time,high-fat feed will be replaced by common feed.The dietary regimen of the intermittent fasting group was complete fasting on the first and second days,followed by free diet for 5 days,then fasting for 2days,and then continued free fasting for 5 days,so that the reciprocation stopped at 4 weeks.The weight of mice was measured weekly,blood sugar was measured every 4 weeks.After 4 weeks of intermittent fasting intervention,blood samples were taken to further detect the expression of insulin and glucagon in serum,MDA,SOD and 8-OHdG in pancreas tissue.Results: At 8 weeks,the mouse model was successfully established.After 4 weeks of intermittent fasting intervention,serum insulin secretion decreased,but glucagon did not change significantly;blood sugar did not change significantly,HOMA-IR improved significantly,and oxidative stress products MDA and 8-OHdG in pancreas tissue were higher than those in DIO group.Part 3: The effect of intermittent fasting on autophagy in obese C57BL/6J mice Aim: To investigate the effect of intermittent fasting on autophagy in pancreatic islet in obese mice.Methods: The pancreatic tissues of the second part were examined by HE staining,the expressionsof Beclin-1 and LC-3 were detected by immunohistochemistry,and the expressions of autophagyrelated proteins Beclin-1,LC-3,SIRT1 and FoxO1 were detected by Western blotting and real-time PCR.Results: HE staining showed that the cells in the islets of obese group showed atrophy and necrosis in a few cells,while the cells in intermittent group showed degeneration and no obvious necrosis.Immunohistochemistry showed that the expression of autophagy marker protein Beclin-1 and LC-3mainly concentrated in the islets of pancreas.The expression of autophagy marker protein Beclin-1 and LC-3 decreased significantly in DIO group,but increased significantly in the intermittent fasting group.Western blotting and qPCR detection showed that the expression of autophagy the expression of autophagy-related proteins Beclin-1 and LC-3 in the intermittent fasting intervention group was significantly higher than that in the obese group,while the expression of SIRT1 in the signaling pathway was higher than that in the DIO group,while the expression of FoxO1 was lower than that in the DIO group.Conclusion: Intermittent fasting can improve insulin resistance by up-regulating SIRT1 expression,reducing FoxO1 level. |
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