title: Hypoxia-induced intrauterine growth restriction increases the susceptibility of rats to high-fat diet-induced metabolic syndrome.
abstract: OBJECTIVE
  It is recognized that there is a remarkable variability in the systemic response to high-fat (HF) diets that cannot be completely explained by genetic factors. In addition, pregnancy complications leading to intrauterine growth restriction (IUGR) have been associated with an increased risk of developing metabolic syndrome (MetS) later in life. Thus, we hypothesized that offspring born with IUGR exhibit permanent metabolic changes that make them more susceptible to HF diet-induced MetS.
  
  
  METHODS
  SD rats born normal (control) or with hypoxia-induced IUGR were randomized to low-fat (10% fat) or HF (45% fat) diets. After 9 weeks of feeding, physiological and molecular pathways involved in the MetS were evaluated.
  
  
  RESULTS
  IUGR offspring exhibited decreased energy intake and physical activity relative to controls. In offspring fed a HF diet, IUGR was associated with decreased total body fat content, a relative increase in intra-abdominal fat deposition and adipocyte size, an increase in fasting plasma concentrations of leptin, triglyceride and free fatty acids, and an increased concentration of triglycerides and ceramides in both liver and skeletal muscle. These changes in lipid homeostasis were accompanied by in vivo insulin resistance and impaired glucose tolerance and associated with increased phosphorylation of protein kinase C , inhibition of insulin receptor substrate 1, and a decreased activation of protein kinase B (PKB; also known as Akt) in liver and skeletal muscle in response to insulin.
  
  
  CONCLUSIONS
  IUGR enhances specific deleterious metabolic responses to a HF diet. Our results suggest that offspring born with IUGR may require special attention and follow-up to prevent the early onset of MetS.
authors.affiliation: Department of Physiology, University of Alberta, Edmonton, Canada.
authors.forename: Christian F
authors.initials: CF
authors.lastname: Rueda-Clausen
authors.forename: Vernon W
authors.initials: VW
authors.lastname: Dolinsky
authors.forename: Jude S
authors.initials: JS
authors.lastname: Morton
authors.forename: Spencer D
authors.initials: SD
authors.lastname: Proctor
authors.forename: Jason R B
authors.initials: JR
authors.lastname: Dyck
authors.forename: Sandra T
authors.initials: ST
authors.lastname: Davidge
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D001823:Body Composition; D016207:Cytokines / Q000097:blood; D004041:Dietary Fats / Q000378:metabolism*; D004198:Disease Susceptibility / Q000209:etiology / Q000378:metabolism*; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology / Q000378:metabolism*; D018149:Glucose Intolerance / Q000378:metabolism; D000860:Hypoxia / Q000150:complications* / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000209:etiology / Q000378:metabolism*; D011247:Pregnancy; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D016207:Cytokines; D004041:Dietary Fats; D007328:Insulin; D008055:Lipids