Neonatal overfeeding in mice aggravates the development of methionine and choline-deficient diet-induced steatohepatitis in adulthood  

作　　者：Juan Du Xuemei Cao Junlin Diao Qijuan Zhang Chuan Peng Jibin Li Xiaoqiu Xiao 

机构地区：[1]Laboratory of Lipid&Glucose Metabolism,PR China [2]Department of Clinical Nutrition,The First Affiliated Hospital of Chongqing Medical University,PR China [3]School of Public Health and Management,Chongqing Medical University,Research Center for Medicine and Social Development,Innovation Center for Social Risk Governance in Health,Chongqing,400016,PR China

出　　处：《Genes & Diseases》2019年第1期68-77,共10页基因与疾病（英文）

基　　金：The present work was supported by the National Natural Science Foundation of China(grant nos.81270947 and 81570763,to XX);the National Program on Key Basic Research Project of China(973 Program;grant no.2012CB517505,to XX);the Fundamental Science and Advanced Technology Research of Chongqing(Major Project,grant no.CSTC2015jcyjB0146).

摘　　要：Overfeeding in early life is associated with obesity and insulin resistance in adulthood.In the present study,a well-characterized mouse model was used to investigate whether neonatal overfeeding increases susceptibility to the development of non-alcoholic steatohepatitis(NASH)following feeding with a methionine and choline-deficient(MCD)diet.Neonatal overfeeding was induced by adjusting litters to 3 pups per dam(small litter size,SL)in contrast to 10 pups per dam as control(normal litter size,NL).At 11 weeks of age,mice were fed with standard(S)or a methionine and choline-deficient(MCD)diet for 4 weeks.Glucose tolerance tests,tissue staining with haematoxylin and eosin,oil-red O and immunohistochemistry for F4/80,reverse transcription-quantitative polymerase chain reaction(RT-qPCR)and western blotting were performed.Compared with NL mice,SL mice exhibited higher body weight gain from 2 weeks of age throughout adulthood,and more profound glucose intolerance as adults.Sterol regulatory element-binding protein 1c and fatty acid synthase mRNA expression levels in liver were upregulated in SL mice at 3 weeks of age.MCD diet induced typical NASH,especially in SL-MCD mice,evidenced by marked fat accumulation,macrovescular steatosis,ballooned hepatocytes,inflammatory cells infiltration and tumour necrosis factor-a mRNA upregulation in the liver,as well as increased alanine aminotransferase and aspartate aminotransferase levels in the serum.There were no significant differences in liver fibrosis in all groups.Overfeeding during early life exhibited effect with administration of MCD diet in inducing adverse effects on the metabolic function and in promoting the progression of NASH in mice,possibly mediated through dysregulated lipid metabolism in hepatocytes and aggravated hepatic inflammation.

关 键 词：Inflammation Insulin resistance Neonatal overfeeding Non-alcoholic steatohepatitis Obesity 

分 类 号：R57[医药卫生—消化系统]