scholarly journals Uteroplacental Insufficiency after Bilateral Uterine Artery Ligation in the Rat: Impact on Postnatal Glucose and Lipid Metabolism and Evidence for Metabolic Programming of the Offspring by Sham Operation

Endocrinology ◽  
2007 ◽  
Vol 149 (3) ◽  
pp. 1056-1063 ◽  
Author(s):  
Kai-Dietrich Nüsken ◽  
Jörg Dötsch ◽  
Manfred Rauh ◽  
Wolfgang Rascher ◽  
Holm Schneider
Keyword(s):  
Lipid Metabolism ◽  
Food Intake ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Intrauterine Growth Restriction ◽  
The Body ◽  
Growth Restriction ◽  
Sham Operation ◽  
Intrauterine Growth ◽  
Glucose And Lipid Metabolism

Ligation of the uterine arteries (LIG) in rats serves as a model of intrauterine growth restriction and subsequent developmental programming of impaired glucose tolerance, hyperinsulinemia, and adiposity in the offspring. Its impact on lipid metabolism has been less well investigated. We compared parameters of glucose and lipid metabolism and glucocorticoid levels in the offspring of dams that underwent either LIG or sham operation (SOP) with those of untreated controls. Blood parameters including insulin, leptin, and visfatin as well as body weight, food intake, and creatinine clearance were recorded up to an age of 30 wk. Glucose tolerance tests were performed, and both leptin and visfatin expression in liver, muscle, and epididymal and mesenteric fat was quantified by RT-PCR. After catch-up growth, weight gain of all groups was similar, despite lower food intake of the LIG rats. LIG offspring showed impaired glucose tolerance from the age of 15 wk as well as elevated glycosylated hemoglobin and corticosterone levels. However, the body fat content of both LIG and SOP animals increased relative to controls, and both showed elevated triglyceride, total cholesterol, and leptin levels as well as a reduced proportion of high-density lipoprotein cholesterol. Thus, use of the LIG model requires both SOP and untreated controls. Although only LIG is associated with impaired glucose tolerance, pathogenic programming of the lipid metabolism can also be induced by SOP. Visfatin does not appear to be involved in the disturbed glucose metabolism after intrauterine growth restriction and may represent only a marker of fat accumulation.

scholarly journals Disruption of the Igf2 gene alters hepatic lipid homeostasis and gene expression in the newborn mouse

2018 ◽  
Vol 315 (5) ◽  
pp. E735-E744 ◽  
Author(s):  
Mary Frances Lopez ◽  
Lingyun Zheng ◽  
Ji Miao ◽  
Reddy Gali ◽  
Grzegorz Gorski ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Growth Factor ◽  
Hepatic Steatosis ◽  
Intrauterine Growth Restriction ◽  
Nutritional Deficiency ◽  
Growth Restriction ◽  
Newborn Mouse ◽  
Hepatic Lipid ◽  
Intrauterine Growth

Newborns with intrauterine growth-restriction are at increased risk of mortality and life-long comorbidities. Insulin-like growth factor-II (IGF2) deficiency in humans, as well as in mice, leads to intrauterine growth restriction and decreased neonatal glycogen stores. The present study aims to further characterize the metabolic and transcriptional consequences of Igf2 deficiency in the newborn. We found that, despite being born significantly smaller than their wild-type ( Igf2+/+) littermates, brain size was preserved in Igf2 knockout ( Igf2−/−), consistent with nutritional deficiency. Histological and triglyceride analyses of newborn livers revealed that Igf2−/− mice are born with hepatic steatosis. Gene expression analysis in Igf2−/− newborn livers showed an alteration of genes known to be dysregulated in chronic caloric restriction, including the most upregulated gene, serine dehydratase. Multiple genes connected with lipid metabolism and/or hepatic steatosis were also upregulated. Ingenuity Pathway Analysis confirmed that the biological functions most altered in livers of Igf2−/− newborns are related to lipid metabolism, with the top upstream regulator predicted to be the peroxisome proliferator-activated receptor alpha, a master regulator of hepatic lipid and carbohydrate homeostasis. Together, our data indicate that Igf2 deficiency leads to a newborn phenotype strongly reminiscent of nutritional deficiency, including growth retardation, increased brain/body weight ratio, hepatic steatosis, and characteristic changes in hepatic gene expression. We propose that in addition to its growth factor proliferating functions, Igf2 may also regulate growth by altering the expression of genes that control nutrient metabolism in the newborn.

scholarly journals Intrauterine Growth Restriction Increases TNFαand Activates the Unfolded Protein Response in Male Rat Pups

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Emily S. Riddle ◽  
Michael S. Campbell ◽  
Brook Y. Lang ◽  
Ryann Bierer ◽  
Yan Wang ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Insulin Signaling ◽  
Intrauterine Growth Restriction ◽  
Male Rat ◽  
Intrauterine Growth ◽  
Unfolded Protein ◽  
Rat Pups ◽  
The Unfolded Protein Response ◽  
Protein Response

Intrauterine growth restriction (IUGR) programs adult disease, including obesity and insulin resistance. Our group previously demonstrated that IUGR dysregulates adipose deposition in male, but not female, weanling rats. Dysregulated adipose deposition is often accompanied by the release of proinflammatory signaling molecules, such as tumor necrosis factor alpha (TNFα). TNFαcontributes to adipocyte inflammation and impaired insulin signaling. TNFαhas also been implicated in the activation of the unfolded protein response (UPR), which impairs insulin signaling. We hypothesized that, in male rat pups, IUGR would increase TNFα, TNFR1, and components of the UPR (Hspa5, ATF6, p-eIF2α, and Ddit3) prior to the onset of obesity. We further hypothesized that impaired glucose tolerance would occur after the onset of adipose dysfunction in male IUGR rats. To test this hypothesis, we used a well-characterized rat model of uteroplacental insufficiency-induced IUGR. Our primary findings are that, in male rats, IUGR (1) increased circulating and adipose TNFα, (2) increased mRNA levels of UPR components as well as p-eIF2a, and (3) impaired glucose tolerance after observed TNFαincreased and after UPR activation. We speculate that programmed dysregulation of TNFαand UPR contributed to the development of glucose intolerance in male IUGR rats.

scholarly journals Prenatal Skeletal Muscle Transcriptome Analysis Reveals Novel MicroRNA-mRNA Networks Associated with Intrauterine Growth Restriction in Pigs

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1007
Author(s):  
Asghar Ali ◽  
Eduard Murani ◽  
Frieder Hadlich ◽  
Xuan Liu ◽  
Klaus Wimmers ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fetal Growth ◽  
Intrauterine Growth Restriction ◽  
Muscle Development ◽  
Muscle Growth ◽  
The Body ◽  
Growth Restriction ◽  
Economic Losses ◽  
Biological Processes ◽  
Intrauterine Growth

Intrauterine growth restriction (IUGR) occurs in 15–20% of pig neonates and poses huge economic losses to the pig industry. IUGR piglets have reduced skeletal muscle growth, which may persist after birth. Prenatal muscle growth is regulated by complex molecular pathways that are not well understood. MicroRNAs (miRNAs) have emerged as the main regulators of vital pathways and biological processes in the body. This study was designed to identify miRNA–mRNA networks regulating prenatal skeletal muscle development in pigs. We performed an integrative miRNA–mRNA transcriptomic analysis in longissimus dorsi muscle from IUGR fetuses and appropriate for gestational age (AGA) fetuses at 63 days post conception. Our data showed that 47 miRNAs and 3257 mRNAs were significantly upregulated, and six miRNAs and 477 mRNAs were significantly downregulated in IUGR compared to AGA fetuses. Moreover, 47 upregulated miRNAs were negatively correlated and can potentially target 326 downregulated genes, whereas six downregulated miRNAs were negatively correlated and can potentially target 1291 upregulated genes. These miRNA–mRNA networks showed enrichment in biological processes and pathways critical for fetal growth, development, and metabolism. The miRNA–mRNA networks identified in this study can potentially serve as indicators of prenatal fetal growth and development as well as postnatal carcass quality.

Intrauterine Growth Restriction Modifies the Accumbal Dopaminergic Response to Palatable Food Intake

Neuroscience ◽  
2019 ◽  
Vol 400 ◽  
pp. 184-195 ◽  
Author(s):  
D.P. Laureano ◽  
M.B. Alves ◽  
P.M. Miguel ◽  
T.D. Machado ◽  
A.R. Reis ◽  
...  
Keyword(s):  
Food Intake ◽  
Intrauterine Growth Restriction ◽  
Growth Restriction ◽  
Palatable Food ◽  
Intrauterine Growth

Comparison of two models of intrauterine growth restriction for early catch-up growth and later development of glucose intolerance and obesity in rats

2010 ◽  
Vol 298 (1) ◽  
pp. R141-R146 ◽  
Author(s):  
Yasaman Shahkhalili ◽  
Julie Moulin ◽  
Irene Zbinden ◽  
Olivier Aprikian ◽  
Katherine Macé
Keyword(s):  
Body Weight ◽  
Birth Weight ◽  
Food Intake ◽  
Glucose Intolerance ◽  
Intrauterine Growth Restriction ◽  
Food Restriction ◽  
Plasma Insulin ◽  
Growth Restriction ◽  
Intrauterine Growth ◽  
Catch Up

Two models of intrauterine growth restriction, maternal food restriction (FR), and dexamethasone (DEX) exposure were compared for early postnatal catch-up growth and later development of glucose intolerance and obesity in Sprague-Dawley rats. Mated dams were randomly divided into three groups at 10 days gestational age. Group FR was food restricted (50% of nongestating rats) during the last 11 days of gestation; Group DEX received DEX injections during the last week of gestation, and Group CON, the control group, had no intervention. Birth weight, catch-up growth, body weight, and food intake were measured in male offspring for 22 wk. Body composition, blood glucose, and plasma insulin in response to a glucose load were assessed at 8, 16, and 22 wk. Pups from both FR and DEX dams had similarly lower birth weights than CON (22% and 25%, P < 0.0001), but catch-up growth, which occurred during the suckling period, was much more rapid in FR than DEX offspring (6 vs. 25 days, 95% CI). Postweaning, there were no significant differences between groups in food intake, body weight, body fat, and plasma insulin, but baseline plasma glucose at 22 wk and 2-h glucose area-under-the-curve at 8 and 22 wk were greater only in FR vs. CON offspring ( P < 0.05), thereby contrasting with the lack of significant differences between DEX and CON. These results suggest that prenatal food restriction is a more sensitive model than DEX exposure for studies aimed at investigating the link between low birth weight, early postnatal catch-up growth, and later development of glucose intolerance.

Perinatal glucose tolerance after intrauterine growth restriction in the late-gestation ovine fetus

2004 ◽  
Vol 191 (6) ◽  
pp. S132
Author(s):  
Philippe Deruelle ◽  
Iva Gueorguieva ◽  
Berengere Sicot De Jenlis ◽  
Sophie Jaillard ◽  
Jacques Weill ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Intrauterine Growth Restriction ◽  
Growth Restriction ◽  
Late Gestation ◽  
Intrauterine Growth ◽  
Ovine Fetus
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