Maternal Nutrient Restriction During Late Gestation and Early Postnatal Growth in Sheep Differentially Reset the Control of Energy Metabolism in the Gastric Mucosa

Abstract

Fetal growth restriction followed by accelerated postnatal growth contributes to impaired metabolic function in adulthood. The extent to which these outcomes may be mediated centrally within the hypothalamus, as opposed to in the periphery within the digestive tract, remains unknown. In a sheep model, we achieved intrauterine growth restriction experimentally by maternal nutrient restriction (R) that involved a 40% reduction in food intake through late gestation. R offspring were then either reared singly to accelerate postnatal growth (RA) or as twins and compared with controls also reared singly. From weaning, all offspring were maintained indoors until adulthood. A reduced litter size accelerated postnatal growth for only the first month of lactation. Independently from postnatal weight gain and later fat mass, R animals developed insulin resistance as adults. However, restricted accelerated offspring compared with both the control accelerated and restricted restricted offspring ate less and had higher fasting plasma leptin as adults, an adaptation which was accompanied by changes in energy sensing and cell proliferation within the abomasum. Additionally, although fetal restriction down-regulated gene expression of mammalian target of rapamycin and carnitine palmitoyltransferase 1-dependent pathways in the abomasum, RA offspring compensated for this by exhibiting greater activity of AMP-activated kinase-dependent pathways. This study demonstrates a role for perinatal nutrition in the peripheral control of food intake and in energy sensing in the gastric mucosal and emphasizes the importance of diet in early life in regulating energy metabolism during adulthood.

The Influence of Sex on Early Stage Markers of Kidney Dysfunction in Response to Juvenile Obesity

“…Both diastolic and systolic blood pressure measurements were determined at 16 months with a standard blood pressure measuring device under sedation when scanned using dual x-ray absorptiometry. 17 This gave blood pressure values that are in accordance with those recorded in conscious adult sheep. 15 Then at 17 months, 5-mL blood samples were withdrawn after an overnight fast into lithium heparin tubes and centrifuged at 2500g for 10 minutes at 4°C to obtain plasma.…”

Effect of pre- and postnatal growth and post-weaning activity on glucose metabolism in the offspring

“…In an absence of adult obesity, the detrimental effects of IUGR appeared to be much less pronounced. We have, therefore, indicated the important association between raised plasma insulin and in utero programed changes of hypothalamic sensitivity observed previously following juvenile-onset obesity (Sebert et al 2011). Both acute and chronic reductions in maternal food intake in late gestation stimulate maternal catabolism resulting in hypoglycemia, ketoacidosis (Herrera & Amusquivar 2000, Tygesen et al 2008, and an increased lipolysis (Symonds et al 1989).…”

“…The experimental nutritional intervention has previously been described in detail (Sebert et al 2011). In brief, 28 Bluefaced Leicester cross Swaledale twin-bearing sheep (ovis) were individually housed at 100 days of gestation (dGA) and, at 110 dGA, randomly allocated to the experimental groups (Fig.…”

“…This is important as many human studies indicate that the long-term impact of reduced birth size, in both term and preterm infants, can be dependent on early postnatal growth (Singhal et al 2003, Stettler et al 2003. In sheep, the relative importance of enhanced postnatal growth on long-term outcomes has not been widely examined, although, when combined with IUGR, accelerated postnatal growth differentially affects energy sensing within the stomach and hypothalamus (Sebert et al 2011). The post-weaning environment is an additional factor that appears to determine the magnitude of the phenotypic response to alterations in maternal diet in pregnancy in rodents (Desai et al 2007).…”

Interaction entre facteurs d’environnement et fonds génétique dans le diabète de type 2

“…De fait, la sous-nutrition maternelle est responsable de la naissance de nouveau-nés de faibles poids, ce qui est, grossièrement, le reflet d'un retard de croissance plus général (retard de croissance intra-utérin, RCIU). Plus spécifiquement, ces altérations toucheraient les organes capables de recueillir et d'intégrer les signaux hormonaux et métaboliques, tels que le pancréas, le cerveau ou le tractus gastrointestinal [9][10][11][12]. Ainsi, la sous-nutrition foetale en milieu et en fin de gestation est associée à une augmentation du risque de développer un défaut métabolique, tel que l'obésité et le diabète, notamment [9].…”