ABSTRACT
BACKGROUND: Intrauterine growth restriction (IUGR) is known to affect the risk of adult diseases. Consumption of lipogenic fructose is increasing, and it is used as an enhancer of metabolic syndrome in rat experiments. The effects of IUGR, postnatal fructose diet, and their interaction on the lipid profile and adiposity were studied in adult rats. METHODS: IUGR was induced by providing pregnant rats with 50% of daily food intake. From 1 mo onward, half of the offspring received a fructose-rich diet and were then followed to the age of 1 and 6 mo, when plasma lipid, glucose, and insulin levels were measured. The adipose tissue was visualized by magnetic resonance imaging at the age of 6 mo. RESULTS: IUGR and fructose diet decreased body weight in adult rats. IUGR increased low-density lipoprotein cholesterol in 6-mo-old rats. The fructose diet evoked hypertriglyceridemia and hyperinsulinemia in both the sexes and decreased fasting glucose levels in female rats. Postnatal fructose diet increased lipid content percentage in the retroperitoneal and intra-abdominal adipose tissues in male rats. Interactions between IUGR and postnatal fructose diet were observed in adult weight in males. CONCLUSION: These results demonstrate the importance of IUGR and fructose diet in adverse changes in lipid and glucose metabolism.
Subject(s)
Body Weight , Dietary Carbohydrates/metabolism , Fetal Growth Retardation/metabolism , Fructose/metabolism , Intra-Abdominal Fat/metabolism , Lipids/blood , Prenatal Exposure Delayed Effects , Adiposity , Age Factors , Animals , Animals, Suckling , Biomarkers/blood , Blood Glucose/metabolism , Dietary Carbohydrates/administration & dosage , Dietary Carbohydrates/adverse effects , Disease Models, Animal , Female , Fetal Growth Retardation/blood , Fetal Growth Retardation/physiopathology , Fructose/administration & dosage , Fructose/adverse effects , Gestational Age , Hyperinsulinism/blood , Hyperinsulinism/etiology , Hypertriglyceridemia/blood , Hypertriglyceridemia/etiology , Insulin/blood , Intra-Abdominal Fat/physiopathology , Magnetic Resonance Imaging , Male , Pregnancy , Rats , Rats, Sprague-DawleyABSTRACT
It has been proposed that fetal exposure to environmental stressors, such as undernutrition, during critical periods of development may lead to adaptations that permanently change the structure and function of the body. These adaptations may be important for immediate survival during fetal development, but can predispose to disease in later life. We designed a pilot study investigating the effect of fetal undernutrition on the obesity-related peptides adiponectin, ghrelin, leptin and resistin levels in rat. We also wanted to explore changes in lipid and insulin metabolism. Sprague-Dawley rats were randomly assigned to three dietary treatment groups on day 4 of gestation. The control group was fed ad libitum and the food-restricted rats received either 75% or 50% of ad libitum food intake until parturition. Serum levels of obesity-related peptides as well as lipid and insulin levels were measured from 1-month-old pups. Serum resistin concentrations were higher in both food-restricted groups and serum adiponectin concentration was lower in the 50% food-restricted group compared to the control group. Serum total cholesterol levels were significantly higher in both food-restricted groups. These results indicate that undernutrition during fetal development may lead to unfavorable changes in obesity-related peptide hormones as well as evoking adverse changes in serum cholesterol levels. The observed changes may predispose to insulin resistance and significantly increase the risk of developing cardiovascular disease in later life.
Subject(s)
Adiponectin/metabolism , Caloric Restriction , Obesity/metabolism , Prenatal Exposure Delayed Effects , Resistin/metabolism , Animals , Cholesterol/blood , Female , Humans , Pilot Projects , Pregnancy , Rats , Rats, Sprague-Dawley , Triglycerides/bloodABSTRACT
BACKGROUND/AIMS: Nutrition during fetal and early postnatal development can have permanent effects on physiology resulting in an increased risk for disease in later life. The aim of this study was to explore changes in gene expression related to maternal energy restriction during pregnancy in rat fetuses and in neonatal rat offspring. METHODS: From day 4 of gestation until parturition, energy-restricted dams received either 75 or 50% of ad libitum food intake. Microarray analyses were performed on whole 13- and 17-day fetuses and 1-day-old pups. Protein and fat contents of the dams' milk were analyzed in the different feeding groups. RESULTS: A surprisingly small number of genes were differentially expressed between the groups, probably due to the strict control of fetal development. Interestingly, the expressions of many pancreatic digestion enzymes were reduced in the 1-day-old pups of the energy-restricted dams. A statistically significant difference in milk protein content was observed on day 1 post-partum between the gestationally food-restricted groups. CONCLUSIONS: The expressions of several genes that may have an important role in the normal development of organs were affected by undernutrition during fetal development. In addition, undernutrition may have affected the function of the exocrine pancreas.
Subject(s)
Diet, Reducing , Fetus/physiology , Gene Expression Profiling , Pregnancy Complications/genetics , Animals , Animals, Newborn/genetics , Calcineurin/genetics , Chymotrypsinogen/genetics , Crystallins/genetics , Cytochrome P-450 Enzyme System/genetics , Female , Fetal Development/genetics , Insulin-Like Growth Factor Binding Proteins/genetics , Milk/chemistry , Oligonucleotide Array Sequence Analysis , Polymerase Chain Reaction/methods , Pregnancy , Pregnancy Complications/etiology , Rats , Rats, Sprague-Dawley , Serine Endopeptidases/geneticsABSTRACT
BACKGROUND: Alterations in the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis are associated with increased cardiovascular morbidity and mortality, but previous studies have yielded conflicting results. In addition, the T1169A polymorphism in the GH1 gene has been associated with IGF-I levels. AIMS: To investigate whether IGF-I concentrations and the T1169A polymorphism of the GH1 gene are associated with cardiovascular risk factors and the intima media thickness (IMT) of the carotid artery. METHODS: Fasting plasma IGF-I concentrations (n=1008) were measured in a large population-based OPERA (Oulu Project Elucidating Risk of Atherosclerosis) cohort. Genotype variants were determined by the restriction fragment length polymorphism method. RESULTS: Low IGF-I concentrations associated with several cardiovascular risk factors including age, adiposity, and high triglyceride, fasting insulin and C-reactive protein concentrations in the analysis of all subjects. In the multivariate models, however, IGF-I concentrations were positively associated with the mean IMT of women (ss=0.127, P=0.009) whereas the association in men was weaker and negative (ss=-0.088, P=0.034). The 1169A allele was associated with low low-density lipoprotein cholesterol in both sexes and with low systolic blood pressure levels in women. CONCLUSIONS: IGF-I concentrations were associated with several traditional cardiovascular risk factors. The observed gender difference in the association between IGF-I concentrations and carotid artery atherosclerosis warrants further study. The GH1 1169A allele may be associated with a favourable metabolic profile.
