Search

Aims: Catch-up growth after a period of nutritional deprivation in adulthood is related to the onset of metabolic disorders. This process involves chromatin remodelling of the Pdx-1 gene in pancreas. The objective of this study was to determine the chromatin remodelling mechanism of GLP-1 analogue Liraglutide upon Pdx-1 in catch-up growth rats in vivo and in vitro., Methods: Five-week-old male specific pathogen free (SPF) Wistar rats were randomly divided into normal group, catch-up growth group and Liraglutide group. Hyperglycemic clamp test and glucose-stimulated insulin secretion test were carried out to evaluate β-cell function in vivo and in vitro. The histone H3 modification changes at the Pdx-1 proximal promoter were assessed by chromatin immunoprecipitation., Results: The catch-up growth state was characterized by less recruitment of histone H3 lysine4 trimethylation and histone H3 acetylation and more recruitment of histone H3 lysine9 dimethylation at the Pdx-1 proximal promoter. Liraglutide treatment reversed these epigenetic changes and increased Pdx-1 expression, which could be abrogated by GLP-1 receptor antagonist Exendin 9-39. The β-cell function of catch-up growth rats was improved after Liraglutide treatment., Conclusions: The protective effects of Liraglutide on pancreatic islet β-cell function may be related to histone H3 modification at the Pdx-1 proximal promoter during catch-up growth and could be used to treat catch-up growth-related metabolic disorders., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: The aim of the study was to analyze the effect of postnatal nutritional rehabilitation on the craniofacial growth in rats with intrauterine growth retardation (IUGR)., Materials and Methods: Wistar rats were assigned to one of the following groups: control, Sham-operated, and IUGR. The IUGR was produced by uterine vessels bending (day 14 of pregnancy). At days 1, 21, 42, 63, and 84 of postnatal life, each animal was X-rayed, and neural and facial length, width and height were measured. Volumetric and morphometric indices were calculated., Results: The decreased maternal-fetal blood flow during the last-third of the gestation period modified cranial size and shape of both sexes at birth., Discussion: Postnatal nutritional rehabilitation is not fully sufficient to reverse the prenatal growth retardation. There are specific responses depending on the sex and the age of the IUGR pups. Regardless of the changes in size, the shape is not modified during all the postnatal period.

The effects of undernutrition during pregnancy on prenatal and postnatal development of the offspring were evaluated in sows with obesity/leptin resistance. Females were fed, from day 35 of pregnancy onwards, a diet fulfilling either 100% (group control, n=10) or 50% of the nutritional requirements (group underfed, n=10). In the control group, maternal body weight increased during pregnancy (P<0.05) while it decreased or remained steady in the underfed group. At days 75 and 100 of gestation, plasma triglycerides were lower but urea levels were higher in restricted than in control sows (P<0.05 for both). Assessment of the offspring indicated that the trunk diameter was always smaller in the restricted group (P<0.01 at day 50, P<0.005 at days 75 and 100 and P<0.0001 at birth) while head measurements were similar through pregnancy, although smaller in the restricted than in the control group at birth (P<0.05). Newborns from restricted sows were also lighter than offspring from control females (P<0.01) and had higher incidence of growth retardation (P<0.01). Afterwards, during lactation, early postnatal growth in restricted piglets was modulated by gender. At weaning, males from restricted sows were still lighter than their control counterparts (P<0.05), while females from control and underfed sows were similar. Thus, the current study indicates a gender-related differential effect in the growth patterns of the piglets, with females from restricted sows evidencing catch-up growth to neutralise prenatal retardation and reaching similar development than control counterparts.

Objective: To describe the motivators and barriers to the adoption of a healthy postpartum lifestyle after a pregnancy complicated by preeclampsia, intrauterine growth restriction, and/or gestational diabetes., Methods: Thirty-six women with complicated pregnancies participated in six focus-group interviews that aimed to explore the perceptions of modifiable determinants of postpartum lifestyle., Results: Although women expressed that they intended to live a healthy postpartum lifestyle, it was generally not achieved. The motivators included improving their own current health condition as well as modeling a healthy lifestyle for their children. Important barriers were reported to be lack of knowledge, poor recovery, and lack of professional support after delivery., Conclusions: The reported motivators and barriers can be used to develop a postpartum lifestyle intervention.

Intrauterine growth restriction (IUGR) is closely linked with metabolic diseases, appetite disorders and obesity at adulthood. Leptin, a major adipokine secreted by adipose tissue, circulates in direct proportion to body fat stores, enters the brain and regulates food intake and energy expenditure. Deficient leptin neuronal signalling favours weight gain by affecting central homeostatic circuitry. The aim of this study was to determine if leptin resistance was programmed by perinatal nutritional environment and to decipher potential cellular mechanisms underneath.We clearly demonstrated that 5 months old IUGR rats develop a decrease of leptin sentivity, characterized by no significant reduction of food intake following an intraperitoneal injection of leptin. Apart from the resistance to leptin injection, results obtained from IUGR rats submitted to rapid catch-up growth differed from those of IUGR rats with no catch-up since we observed, for the first group only, fat accumulation, increased appetite for food rich in fat and increased leptin synthesis. Centrally, the leptin resistant state of both groups was associated with a complex and not always similar changes in leptin receptor signalling steps. Leptin resistance in IUGR rats submitted to rapid catch-up was associated with alteration in AKT and mTOR pathways. Alternatively, in IUGR rats with no catch-up, leptin resistance was associated with low hypothalamic expression of LepRa and LepRb. This study reveals leptin resistance as an early marker of metabolic disorders that appears before any evidence of body weight increase in IUGR rats but whose mechanisms could depend of nutritional environment of the perinatal period.

Fetal growth restriction is associated with reduced pancreatic β-cell mass, contributing to impaired glucose tolerance and diabetes. Exercise training increases β-cell mass in animals with diabetes and has long-lasting metabolic benefits in rodents and humans. We studied the effect of exercise training on islet and β-cell morphology and plasma insulin and glucose, following an intraperitoneal glucose tolerance test (IPGTT) in juvenile and adult male Wistar-Kyoto rats born small. Bilateral uterine vessel ligation performed on day 18 of pregnancy resulted in Restricted offspring born small compared with sham-operated Controls and also sham-operated Reduced litter offspring that had their litter size reduced to five pups at birth. Restricted, Control, and Reduced litter offspring remained sedentary or underwent treadmill running from 5 to 9 or 20 to 24 wk of age. Early life exercise increased relative islet surface area and β-cell mass across all groups at 9 wk, partially restoring the 60-68% deficit (P < 0.05) in Restricted offspring. Remarkably, despite no further exercise training after 9 wk, β-cell mass was restored in Restricted at 24 wk, while sedentary littermates retained a 45% deficit (P = 0.05) in relative β-cell mass. Later exercise training also restored Restricted β-cell mass to Control levels. In conclusion, early life exercise training in rats born small restored β-cell mass in adulthood and may have beneficial consequences for later metabolic health and disease.

The effect of early intervention with a peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist on skeletal muscle GLUT4 translocation and insulin signaling was examined in intrauterine (IUGR) and postnatal (PNGR) growth-restricted pregestational female rat offspring. Rosiglitazone [11 mumol/day provided from postnatal day (PN)21 to PN60] improved skeletal muscle insulin sensitivity and GLUT4 translocation in prenatal nutrient restriction [50% calories from embryonic day (e)11 to e21; IUGR] with (IUGR+PNGR) and without (IUGR) postnatal nutrient restriction (50% calories from PN1 to PN21; PNGR) similar to that of control (ad libitum feeds throughout; Con) (n = 6 each). This was accomplished by diminished basal and improved insulin-responsive GLUT4 association with the plasma membrane in IUGR, IUGR+PNGR, and PNGR mimicking that in Con (P < 0.005). While no change in p85-phosphatidylinositol 3-kinase (PI3-K) and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was observed, a decrease in protein tyrosine phosphatase 1B (PTP1B; P < 0.0002) and SH2-containing protein tyrosine phosphatase 2 (SHP2; P < 0.05) contributing to the rosiglitazone-induced insulin sensitivity was seen only in IUGR+PNGR. In contrast, an increase in phosphorylated 5'-adenosine monophosphate kinase (pAMPK; P < 0.04) and insulin responsiveness of phosphorylated phosphoinositide-dependent protein kinase-1 (pPDK1; P < 0.05), pAkt (P < 0.01), and particularly pPKCzeta (P < 0.0001) and its corresponding enzyme activity (P < 0.005) were observed in all four experimental groups. We conclude that early introduction of PPARgamma agonist improved skeletal muscle activation of AMPK and insulin signaling, resulting in insulin-independent AMPK and insulin-responsive GLUT4 association with plasma membranes in IUGR, IUGR+PNGR, and PNGR adult offspring, similar to that of Con. These findings support a role for insulin sensitizers in preventing the subsequent development of gestational or type 2 diabetes mellitus in intrauterine and postnatal growth-restricted offspring.

The authors investigated the association between intrauterine growth and intellectual disability (ID). The appropriateness of intrauterine growth was assessed using percentage of optimal birth weight, a measure that accounts for gestational age, maternal height, parity, and infant sex. Using population-based record linkage, singleton Caucasian and Aboriginal children born in Western Australia in 1983-1992 and alive in 2002 with ID of unknown cause (n = 2,625) were compared with children without ID (n = 217,252). The odds of ID increased with less-than-optimal intrauterine growth. In Caucasian children, after adjustment for sociodemographic factors, severe growth restriction was associated with development of mild-moderate ID among preterm births (<37 weeks) (odds ratio (OR) = 1.71, 95% confidence interval (CI): 1.06, 2.77) and term births (> or =37 weeks) (OR = 2.42, 95% CI: 1.88, 3.12) and with severe ID (OR = 4.79, 95% CI: 2.59, 8.83) among term births. Effects were similar among Aboriginal children. Severe growth restriction (OR = 3.2, 95% CI: 1.3, 7.9) and poor head growth (OR = 3.6, 95% CI: 1.4, 9.0) were independently associated with severe ID. Infants with excess intrauterine growth were more likely to be diagnosed with ID associated with autism spectrum disorder (OR = 2.36, 95% CI: 0.93, 6.03). These findings suggest that inappropriate intrauterine growth, less than or greater than optimal birth weight, is associated with development of ID.

Advances in neonatal medicine have resulted in the increased survival of infants at lower and lower birth weight. While these medical success stories highlight the power of medical technology to save many of the tiniest infants at birth, serious questions remain about how these infants will develop and whether they will have normal, productive lives. Low birth weight children can be born at term or before term and have varying degrees of social and medical risk. Because low birth weight children are not a homogeneous group, they have a broad spectrum of growth, health, and developmental outcomes. While the vast majority of low birth weight children have normal outcomes, as a group they generally have higher rates of subnormal growth, illnesses, and neurodevelopmental problems. These problems increase as the child's birth weight decreases. With the exception of a small minority of low birth weight children with mental retardation and/or cerebral palsy, the developmental sequelae for most low birth weight infants include mild problems in cognition, attention, and neuromotor functioning. Long-term follow-up studies conducted on children born in the 1960s indicated that the adverse consequences of being born low birth weight were still apparent in adolescence. Adverse sociodemographic factors negatively affect developmental outcomes across the continuum of low birth weight and appear to have far greater effects on long-term cognitive outcomes than most of the biological risk factors. In addition, the cognitive defects associated with social or environmental risks become more pronounced as the child ages. Enrichment programs for low birth weight children seem to be most effective for the moderately low birth weight child who comes from a lower socioeconomic group. Continued research and attempts to decrease the rate of low birth weight and associated perinatal medical sequelae are of primary importance. Ongoing documentation of the long-term outcome of low birth weight children needs to be mandated, as does the implementation of environmental enrichment programs to help ameliorate the long-term consequences for infants who are born low birth weight.