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

Publication date: Available online 5 January 2018Source: Genes & DiseasesAuthor(s): Juan Du, Xuemei Cao, Junlin Diao, Qijuan Zhang, Chuan Peng, Jibin Li, Xiaoqiu XiaoAbstractOverfeeding 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 infi...
Source: Genes and Diseases - Category: Genetics & Stem Cells Source Type: research