title: Long-term effect of early postnatal overnutrition on insulin resistance and serum fatty acid profiles in male rats.
abstract: BACKGROUND
  Increasing evidence suggests that overnutrition during the early postnatal period, a critical window of development, increases the risk of adult-onset obesity and insulin resistance. In this study, we investigated the impact of overnutrition during the suckling period on body weight, serum biochemistry and serum fatty acid metabolomics in male rats.
  
  
  METHODS
  Rats raised in small litters (SL, 3 pups/dam) and normal litters (NL, 10 pups/dam) were used to model early postnatal overnutrition and control, respectively. Serum glucose, triglyceride, high-density lipoprotein-cholesterol, free fatty acid, insulin and leptin concentrations were assayed using standard biochemical techniques. Serum fatty acids were identified and quantified using a gas chromatography-mass spectrometry-based metabolomic approach. mRNA and protein levels of key components of the insulin receptor signaling pathway were measured in epididymal fat and gastrocnemius muscle by quantitative PCR and western blotting.
  
  
  RESULTS
  SL rats were 37.3 % and 15.1 % heavier than NL rats at weaning and 16-weeks-old, respectively. They had increased visceral fat mass, adult-onset insulin resistance and glucose intolerance as well as elevated serum levels of free fatty acids and triglycerides. All detectable fatty acids were elevated in the serum of SL pups at weaning compared to NL controls, and significant increases in the levels of four fatty acids (palmitic acid, palmitoleic acid, oleic acid and arachidonic acid) persisted into adulthood. Moreover, a significantly positive correlation was identified between an insulin resistance index (HOMA-IR) and concentrations of myristic, palmitic, palmitoleic and oleic acid in serum at postnatal 16 weeks. Early postnatal overnutrition also resulted in a significant downregulation of insulin receptor substrate-1 (Irs-1), protein kinase B (Akt2) and glucose transporter 4 (Glut4) at the protein level in epididymal fat of SL rats at 16 weeks, accompanied by decreased mRNA levels for Irs-1 and Glut4. In gastrocnemius muscle, Akt2 and Glut4 mRNA and Glut4 protein levels were significantly decreased in SL rats.
  
  
  CONCLUSIONS
  This study demonstrates that early postnatal overnutrition can have long-lasting effects on body weight and serum fatty acid profiles and can lead to impaired insulin signaling pathway in visceral white adipose tissue and skeletal muscle, which may play a major role in IR.
authors: Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China. fionabei@163.com.|Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, 1665 Kongjiang Road, Shanghai, 200092, China. fionabei@163.com.|Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China. fionabei@163.com.
authors: Fei
authors: F
authors: Bei
authors: Shanghai Center for Bioformation Technology, 1278 Keyuan Road, Shanghai, 201203, China. jiajia@scbit.org.
authors: Jia
authors: J
authors: Jia
authors: Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201203, China. yqjia1961@126.com.
authors: Yi-Qun
authors: YQ
authors: Jia
authors: Department of Neonatology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Road, Shanghai, 200127, China. jianhs@126.com.
authors: Jian-Hua
authors: JH
authors: Sun
authors: Department of Neonatology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Road, Shanghai, 200127, China. liangfei.0719@163.com.
authors: Fei
authors: F
authors: Liang
authors: School of Public Health, Physiotherapy & Sports Science, University College Dublin, Belfield, Dublin, 4, Ireland. zhongyi.yu@ucdconnect.ie.
authors: Zhong-Yi
authors: ZY
authors: Yu
authors: Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China. caiw1978@163.com.|Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, 1665 Kongjiang Road, Shanghai, 200092, China. caiw1978@163.com.|Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China. caiw1978@163.com.
authors: Wei
authors: W
authors: Cai
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005786:Gene Expression Regulation; D051275:Glucose Transporter Type 4 / Q000097:blood / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000097:blood / Q000235:genetics; D055504:Insulin Receptor Substrate Proteins / Q000097:blood / Q000235:genetics; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood / Q000235:genetics; D008075:Lipoproteins, HDL / Q000097:blood; D008098:Litter Size; D008297:Male; D009765:Obesity / Q000097:blood / Q000235:genetics*; D044343:Overnutrition / Q000097:blood / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000097:blood / Q000235:genetics; D012333:RNA, Messenger / Q000097:blood* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D051275:Glucose Transporter Type 4; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D020738:Leptin; D008075:Lipoproteins, HDL; D012333:RNA, Messenger; C495694:Slc2a4 protein, rat; D014280:Triglycerides; C494923:Akt2 protein, rat; D051057:Proto-Oncogene Proteins c-akt