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作 者:Ruchi Tripathi Sanjay Kumar Banerjee Jay Prakash Nirala Rajani Mathur
机构地区:[1]Department of Pharmacology,Delhi Institute of Pharmaceutical Sciences & Research,Delhi Pharmaceutical Sciences and Research University(DPSR-U)),New Delhi,INDIA [2]Drug Discovery Research Centre,Translational Health Science and Technology Institute,Faridabad,INDIA [3]Department of Biotechnology,National Institute of Pharmaceutical Education and Research,Guwahati,INDIA [4]School of Environmental Sciences,Jawaharlal Nehru University,New Delhi,INDIA
出 处:《Biomedical and Environmental Sciences》2023年第11期1045-1058,共14页生物医学与环境科学(英文版)
基 金:supported by the Indian Council of Medical Research(ICMR)in New Delhi.(Sanction NO:5/10/FR/13/2015-RBMH)。
摘 要:Objective In this study,the combined effect of two stressors,namely,electromagnetic fields(EMFs)from mobile phones and fructose consumption,on hypothalamic and hepatic master metabolic regulators of the AMPK/SIRT1-UCP2/FOXO1 pathway were elucidated to delineate the underlying molecular mechanisms of insulin resistance.Methods Weaned Wistar rats(28 days old)were divided into 4 groups:Normal,Exposure Only(ExpO),Fructose Only(FruO),and Exposure and Fructose(EF).Each group was provided standard laboratory chow ad libitum for 8 weeks.Additionally,the control groups,namely,the Normal and FruO groups,had unrestricted access to drinking water and fructose solution(15%),respectively.Furthermore,the respective treatment groups,namely,the ExpO and EF groups,received EMF exposure(1,760 MHz,2 h/day x 8 weeks).In early adulthood,mitochondrial function,insulin receptor signaling,and oxidative stress signals in hypothalamic and hepatic tissues were assessed using western blotting and biochemical analysis.Result In the hypothalamic tissue of EF,SIRT1,FOXO 1,p-PI3K,p-AKT,ComplexⅢ,UCP2,MnSOD,and catalase expressions and OXPHOS and GSH activities were significantly decreased(P<0.05)compared to the Normal,ExpO,and FruO groups.In hepatic tissue of EF,the p-AMPKα,SIRT1,FOXO1,IRS1,p-PI3K,ComplexⅠ,Ⅱ,Ⅲ,Ⅳ,Ⅴ,UCP2,and MnSOD expressions and the activity of OXPHOS,SOD,catalase,and GSH were significantly reduced compared to the Normal group(P<0.05).Conclusion The findings suggest that the combination of EMF exposure and fructose consumption during childhood and adolescence in Wistar rats disrupts the closely interlinked and multi-regulated crosstalk of insulin receptor signals,mitochondrial OXPHOS,and the antioxidant defense system in the hypothalamus and liver.
关 键 词:EMF-mobile phone FRUCTOSE Childhood-adolescence Insulin receptor signal Mitochondrial OxPHOS Antioxidant system Hypothalamic insulin resistance Hepatic insulin resistance
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