Developmental programming in skeletal muscle in response to overnourishment in the immediate postnatal life in rats

Hung Wen Liu, Saleh Mahmood, Malathi Srinivasan, Dominic J. Smiraglia, Mulchand S. Patel*

*此作品的通信作者

研究成果: 雜誌貢獻期刊論文同行評審

40 引文 斯高帕斯(Scopus)

摘要

Overnourishment during the suckling period [small litter (SL)] results in the development of adult-onset obesity. To investigate the mechanisms that underlie the development of insulin resistance in the skeletal muscle of young and adult female SL rats, the litter size was reduced to 3 female pups/dam (SL) while the control litter had 12 pups/dam from the postnatal Day 3 until Day 21. Protein content, mRNA expression and methylation status of the promoter region of key components in the insulin signaling pathway were determined in the skeletal muscle of SL rats. Overnutrition during the suckling period resulted in increased body weight gains, hyperphagia and adult-onset obesity as well as increased levels of serum insulin, glucose and leptin in SL rats. No differences in the expression of total protein as well as tyrosine phosphorylation of insulin receptor β and glucose transporter 4 (Glut4) were observed in skeletal muscle between two groups at both ages. A significant decrease of total insulin receptor substrate 1 (IRS-1) and an increase in serine phosphorylation of IRS-1 were observed in skeletal muscle from adult SL rats. Hypermethylation of specific cytidyl-3',5'phospho-guanylyl (CpG) dinucleotides in the proximal promoter region was observed for the Irs1 and Glut4 genes, which correlated with the reduction in Irs1 and Glut4 mRNA levels in skeletal muscle of adult SL rats. Our results suggest that epigenetic modifications of the key genes involved in the insulin signaling pathway in skeletal muscle could result in the development of insulin resistance in SL female rats.

原文英語
頁(從 - 到)1859-1869
頁數11
期刊Journal of Nutritional Biochemistry
24
發行號11
DOIs
出版狀態已發佈 - 2013 11月
對外發佈

ASJC Scopus subject areas

  • 內分泌學、糖尿病和代謝
  • 生物化學
  • 分子生物學
  • 營養與營養學
  • 臨床生物化學

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