Timing Of Nutrient Restriction Research Articles

Timing of maternal nutrient restriction during mid- to late-gestation influences net umbilical uptake of glucose and amino acids in adolescent sheep.

Previous research demonstrated that maternal nutrient restriction during mid- to late-gestation influenced net umbilical uptakes of glucose and amino acids in sheep. However, it is unclear how the timing and duration of nutrient restriction during mid- to late-gestation influences net uterine, uteroplacental, and fetal flux of glucose and amino acids. On day 50 of gestation, 41 adolescent ewe lambs carrying singletons were randomly assigned to one of six dietary treatments: 1) 100% of nutrient requirements from days 50 to 90 of gestation (CON; n = 7); 2) 60% of nutrient requirements (RES; n = 7) from days 50 to 90 of gestation; 3) 100% of nutrient requirements from days 50 to 130 of gestation (CON-CON; n = 6); 4) 100% of nutrient requirements from days 50 to 90 of gestation and 60% of nutrient requirements from days 90 to 130 of gestation (CON-RES; n = 7); 5) 60% of nutrient requirements from days 50 to 90 of gestation and 100% of nutrient requirements from days 90 to 130 of gestation (RES-CON; n = 7); or 6) 60% of nutrient requirements from days 50 to 130 of gestation (RES-RES; n = 7). On day 90 (n = 14) and day 130 (n = 27), intraoperative procedures were performed to evaluate uteroplacental blood flows, collect blood samples, and then ewes were euthanized. Net uterine, uteroplacental, and umbilical fluxes of glucose and amino acids were calculated by multiplying blood flow by the arterial-venous concentration difference. Data from days 90 and 130 were analyzed separately using ANOVA in SAS. Maternal nutrient restriction during mid-gestation increased (P = 0.04) net umbilical glucose uptake but, maternal nutrient restriction during late-gestation decreased (P = 0.02) net umbilical glucose uptake. Net umbilical essential amino acid uptake decreased (P = 0.03) with nutrient restriction during mid-gestation; however, net umbilical uptakes of Phe (P = 0.02), Thr (P = 0.05), Met (P = 0.09), and His (P = 0.08) increased or tended to increase after nutrient restriction during late-gestation. These data demonstrate that net umbilical glucose and amino acid uptakes were influenced by the timing of nutrient restriction during mid- to late-gestation. Elevated net umbilical glucose uptake after mid-gestational nutrient restriction was sustained throughout late-gestation, independent of late-gestational feeding level. Long-term adaptations in umbilical glucose uptake may have implications for prenatal and postnatal growth and development of the offspring.

Maternal selenium supplementation and timing of nutrient restriction in pregnant sheep: Impacts on nutrient availability to the fetus1

To determine the effects of maternal Se intake and plane of nutrition during mid or late gestation or both on AA concentrations and metabolite concentrations in the dam and fetus, pregnant ewe lambs (n = 64) were assigned to 1 of 8 treatments arranged in a 2 × 2 × 2 factorial array: Se level [initiated at breeding; adequate (ASe; 3.05 μg/kg of BW) or high (HSe; 70.4 μg/kg of BW)] and nutritional level [100% (control; CON) or 60% (restricted; RES) of NRC recommendations] fed at different times of gestation [d 50 to 90 (mid) or d 91 to 132 (late)]. A blood sample was obtained from each ewe and fetus on d 132 of gestation and used to measure circulating concentrations of glucose, NEFA, blood urea N, and AA. The late RES ewes and their fetuses had less (P ≤ 0.03) circulating glucose compared with late CON ewes and fetuses at d 132; however, no effect (P ≥ 0.14) of diet on the fetal:maternal glucose concentration ratio was observed. Late RES ewes had a smaller (P = 0.01) fetal:maternal NEFA ratio compared with late CON ewes. Ewes fed ASe had a greater (P = 0.01) fetal:maternal blood urea N ratio compared with HSe ewes. Fetal:maternal ratios of total circulating AA, total essential AA, and total nonessential AA were each affected (P ≤ 0.03) by the combination of Se treatment and late gestation nutritional level.

Maternal selenium supplementation and timing of nutrient restriction in pregnant sheep: Effects on maternal endocrine status and placental characteristics1

To determine the effects of maternal Se intake and plane of nutrition during midgestation, late gestation, or both on hormone and metabolite concentrations in the dam and on placental characteristics, pregnant ewe lambs (n = 64) were assigned to 1 of 8 treatments arranged in a 2 x 2 x 2 factorial array: Se level [initiated at breeding; adequate (3.05 microg/kg of BW) or high (70.4 microg/kg of BW)] and nutritional level [100% (control) or 60% (restricted) of NRC recommendations] fed at different times of gestation [d 50 to 90 (midgestation) or d 91 to 130 (late gestation)]. The control ewes had a greater (P = 0.01) percentage change in BW from d 50 than restricted ewes during both mid- and late gestation. Although blood urea N was not affected by either Se or nutritional level, restricted ewes had greater (P = 0.01) concentrations of circulating Se on d 66, 78, 106, 120, and 130 of gestation compared with control ewes. Both Se and timing of the nutritional level affected circulating progesterone; however, only nutritional level affected thyroxine and triiodothyronine concentrations in the dam. Nutrient restriction during late gestation decreased (P <or= 0.01) fetal BW and fetal fluid weight compared with the control ewes (3.75 vs. 4.13 +/- 0.10 kg and 1.61 vs. 2.11 +/- 0.11 kg). Although neither Se nor nutritional level affected (P >or= 0.1) placental, caruncular, or cotyledonary weights, cotyledonary cellular proliferation was decreased (P < 0.05) in ewes receiving a high concentration of Se compared with those receiving adequate Se. In addition, either Se or nutritional level affected vascular endothelial growth factor (VEGFA), VEGFA-receptor 1, VEGFA-receptor 2, and NO synthase mRNA abundance in the cotyledonary tissue. In the caruncular tissue, either Se or nutritional level affected VEGFA-receptor 1, placental growth factor, and NO synthase mRNA abundance. Selenium supplementation and the duration or timing of nutrient restriction appear to influence the endocrine and metabolic status of the ewe, which may influence nutrient transport and placental function.

Adipose Tissue Inflammation: Developmental Ontogeny and Consequences of Gestational Nutrient Restriction in Offspring

Increasing adiposity predisposes to the development of the metabolic syndrome, in part, through adipose tissue dysregulation and inflammation. In addition, offspring nutrient restricted (NR) in utero can exhibit an increased risk of early-onset insulin resistance and obesity, although the mechanisms remain unclear. We aimed to: 1) define adipose tissue ontogeny of key proinflammatory and endoplasmic reticulum stress gene expression from late fetal to early adult life and 2) examine the impact on these genes in gestational nutrient restriction. Pregnant sheep were fed 100% (control) or 50% (NR) of their nutritional requirements between early to mid (28–80 d, term ∼147 d) or late (110–147 d) gestation. In control offspring, toll-like receptor 4 (TLR4), and the macrophage marker CD68, peaked at 30 d of life before declining. IL-18 peaked at 6 months of age, whereas the endoplasmic reticulum chaperone glucose-regulated protein 78 peaked at birth and subsequently declined through postnatal life. TLR4 and CD68 positively correlated with relative adipose tissue mass and with each other. Early to midgestational NR offspring had decreased abundance of IL-18 at 6 months of age. In late gestational NR offspring, CD68 was significantly lower at birth, a pattern that reversed in juvenile offspring, coupled with increased TLR4 abundance. In conclusion, the in utero nutritional environment can alter the adipose tissue inflammatory profile in offspring. This may contribute to the increased risk of insulin resistance or obesity, dependent on the timing of nutrient restriction. Establishing the optimal maternal diet during pregnancy could reduce the burden of later adult disease in the offspring.

Adipose Tissue Inflammation: Developmental Ontogeny and Consequences of Gestational Nutrient Restriction in Offspring

Increasing adiposity predisposes to the development of the metabolic syndrome, in part, through adipose tissue dysregulation and inflammation. In addition, offspring nutrient-restricted (NR) in utero can exhibit an increased risk of early-onset insulin resistance and obesity, although the mechanisms remain unclear. We aimed to: 1) define adipose tissue ontogeny of key proinflammatory and endoplasmic reticulum stress gene expression from late fetal to early adult life and 2) examine the impact on these genes in gestational nutrient restriction. Pregnant sheep were fed 100% (control) or 50% (NR) of their nutritional requirements between early to mid (28-80 d, term approximately 147 d) or late (110-147 d) gestation. In control offspring, toll-like receptor 4 (TLR4), and the macrophage marker CD68, peaked at 30 d of life before declining. IL-18 peaked at 6 months of age, whereas the endoplasmic reticulum chaperone glucose-regulated protein 78 peaked at birth and subsequently declined through postnatal life. TLR4 and CD68 positively correlated with relative adipose tissue mass and with each other. Early to midgestational NR offspring had decreased abundance of IL-18 at 6 months of age. In late gestational NR offspring, CD68 was significantly lower at birth, a pattern that reversed in juvenile offspring, coupled with increased TLR4 abundance. In conclusion, the in utero nutritional environment can alter the adipose tissue inflammatory profile in offspring. This may contribute to the increased risk of insulin resistance or obesity, dependent on the timing of nutrient restriction. Establishing the optimal maternal diet during pregnancy could reduce the burden of later adult disease in the offspring.

Effects of dietary selenium supply and timing of nutrient restriction during gestation on maternal growth and body composition of pregnant adolescent ewes1

The objectives were to examine effects of dietary Se supplementation and nutrient restriction during defined periods of gestation on maternal adaptations to pregnancy in primigravid sheep. Sixty-four pregnant Western Whiteface ewe lambs were assigned to treatments in a 2 x 4 factorial design. Treatments were dietary Se [adequate Se (ASe; 3.05 microg/kg of BW) vs. high Se (HSe; 70.4 microg/kg of BW)] fed as Se-enriched yeast, and plane of nutrition [control (C; 100% of NRC requirements) vs. restricted (R; 60% of NRC requirements]. Selenium treatments were fed throughout gestation. Plane of nutrition treatments were applied during mid (d 50 to 90) and late gestation (d 90 to 130), which resulted in 4 distinct plane of nutrition treatments [treatment: CC (control from d 50 to 130), RC (restricted from d 50 to 90, and control d 90 to 130), CR (control from d 50 to 90, and restricted from d 90 to 130), and RR (restricted from d 50 to 130)]. All of the pregnant ewes were necropsied on d 132 +/- 0.9 of gestation (length of gestation approximately 145 d). Nutrient restriction treatments decreased ewe ADG and G:F, as a result, RC and CR ewes had similar BW and maternal BW (MBW) at necropsy, whereas RR ewes were lighter than RC and CR ewes. From d 90 to 130, the HSe-CC ewes had greater ADG (Se x nutrition; P = 0.05) than did ASe-CC ewes, whereas ADG and G:F (Se x nutrition; P = 0.08) were less for HSe-RR ewes compared with ASe-RR ewes. The CR and RR treatments decreased total gravid uterus weight (P = 0.01) as well as fetal weight (P = 0.02) compared with RC and CC. High Se decreased total (g; P = 0.09) and relative heart mass (g/kg of MBW; P = 0.10), but increased total and relative mass of liver (P < or = 0.05) and perirenal fat (P < or = 0.06) compared with ASe. Total stomach complex mass was decreased (P < 0.01) by all the nutrient restriction treatments, but was reduced to a greater extent in CR and RR compared with RC. Total small intestine mass was similar between RC and CC ewes, but was markedly reduced (P < 0.01) in CR and RR ewes. The mass of the stomach complex and the small and large intestine relative to MBW was greater (P = 0.01) for RC than for CR ewes. Increased Se decreased jejunal DNA concentration (P = 0.07), total jejunal cell number (P = 0.03), and total proliferating jejunal cell number (P = 0.05) compared with ASe. These data indicate that increased dietary Se affected whole-body and organ growth of pregnant ewes, but the results differed depending on the plane of nutrition. In addition, the timing and duration of nutrient restriction relative to stage of pregnancy affected visceral organ mass in a markedly different fashion.

The timing of nutrient restriction during rat pregnancy/lactation alters metabolic syndrome phenotype

Modulation of growth of intrauterine growth restricted (IUGR) newborns causes either adult obesity or normalization of body weight and fat. We investigated the impact of rapid versus delayed catch-up growth of IUGR offspring on glucose and lipid profiles. From 10 days to term gestation and through lactation, control pregnant rats received ad libitum food, whereas study rats were 50% food restricted. Cross-fostering techniques were used to examine effects of food restriction during pregnancy and/or lactation periods. Glucose and lipid profiles were determined in offspring at ages 1 day, 3 weeks, and 9 months. Food restriction during pregnancy produced hypoglycemic IUGR pups. Those permitted rapid catch-up growth demonstrated adult obesity with insulin resistance (hyperglycemia/hyperinsulinemia) and hypertriglyceridemia. Conversely, IUGR exhibiting delayed catch-up growth demonstrated normal adult body weight and insulin deficiency (hyperglycemia/hypoinsulinemia) and elevated cholesterol levels as compared with controls. However, these adult offspring had higher glucose though similar insulin levels as control offspring nursed by food restricted dam. The timing and the rate of IUGR newborn catch-up growth causes markedly altered adult phenotypes. Although delayed newborn catch-up growth may be beneficial in the prevention of adult obesity, there may be significant adverse effects on pancreatic function.

Maternal nutrient restriction alters renal development and blood pressure regulation of the offspring

Studies have shown that the risk of hypertension in adulthood can be affected by the in utero environment. It is established that hypertension is linked to compromised kidney function and that factors affecting organogenesis can increase the risk of later disease. Prostaglandins (PG) and growth factors are known to play an important role in regulating kidney function and renal organogenesis. The extent, however, to which global energy restriction (where all nutrients are reduced) of the mother can programme later blood pressure control or renal PG and growth factor status is unknown. A study is described that aimed to examine the long-term effects of maternal nutrient restriction (NR) and elucidate their relationship with compromised kidney development. First, it was necessary to establish animal models. A sheep model of 50% NR during specific stages of gestation was used to investigate fetal renal development, whilst a rat model of 50% NR throughout pregnancy was used to investigate postnatal kidney development and adult functioning. Molecular analysis has shown that expression of the growth hormone-insulin-like growth factor (GH-IGF) axis is affected by NR in the fetal sheep kidneys, and that changes are dependent on the timing of NR and whether the fetus is a singleton or a twin. Analysis of the kidneys from the rat model has shown nutritional differences in the expression of PG receptors and the enzymes responsible for PG synthesis and degradation that persist into adulthood. In conclusion, NR does affect the GH-IGF and PG axes, and these changes may be important in the nutritional programming of renal functioning and adult blood pressure control.

Impact of maternal undernutrition and fetal number on glucocorticoid, growth hormone and insulin-like growth factor receptor mRNA abundance in the ovine fetal kidney

Epidemiological and animal studies strongly indicate that the environment experienced in utero determines, in part, an individual's likelihood of developing cardiovascular disease in later life. This risk has been further linked to impaired kidney function, as a result of compromised development during fetal life. The present study therefore examined the influence of maternal nutrient restriction (NR), targeted at specific periods of kidney development during early to mid gestation, on the mRNA abundance of receptors for glucocorticoid (GCR), growth hormone (GHR) and insulin-like growth factors-I (IGF-IR) and -II (IGF-IIR), and the IGF-I and -II ligands. This was undertaken in both singleton and twin fetuses. At conception ewes were randomly allocated to either an adequately fed control group or one of four nutrient-restricted groups that were fed half the control amount from 0 to 30, 31 to 65, 66 to 110 or 0 to 110 days gestation. At 110 days gestation all ewes were humanely euthanased and fetal kidneys and surrounding adipose tissue sampled. There was no effect of NR or fetal number on kidney weight, shape or nephron number, but the surrounding fat mass was increased in singleton fetuses exposed to NR for 110 days. An increase in kidney mRNA abundance with NR only occurred in singleton fetuses where IGF-IR mRNA was enhanced with NR from 66-110 days gestation. In twin fetuses, NR had no effect on mRNA abundance. However, for all genes examined mRNA expression was lower in the kidneys of twin compared with singleton fetuses following NR, and the magnitude of the effect was dependent on the timing of NR. In conclusion, the abundance of mRNA for receptors which regulate fetal kidney development are lower in twin animals compared with singletons following periods of nutrient deficiency. This may impact on later kidney development and function.

Timing of nutrient restriction and programming of fetal adipose tissue development.

It is apparent from epidemiological studies that the timing of maternal nutrient restriction has a major influence on outcome in terms of predisposing the resulting offspring to adult obesity. The present review will consider the extent to which maternal age, parity and nutritional restriction at defined stages of gestation can have important effects on fat deposition and endocrine sensitivity of adipose tissue in the offspring. For example, in 1-year-old sheep the offspring of juvenile mothers have substantially reduced fat deposition compared with those born to adult mothers. Offspring of primiparous adult mothers, however, show increased adiposity compared with those born to multiparous mothers. These offspring of multiparous ewes show retained abundance of the brown adipose tissue-specific uncoupling protein 1 at 1 month of age. A stimulated rate of metabolism in brown fat of these offspring may act to reduce adipose tissue deposition in later life. In terms of defined windows of development that can programme adipose tissue growth, maternal nutrient restriction targetted over the period of maximal placental growth results in increased adiposity at term in conjunction with enhanced abundance of mRNA for the insulin-like growth factor-I and -II receptors. In contrast, nutrient restriction in late gestation, coincident with the period of maximal fetal growth, has no major effect on adiposity but results in greater abundance of specific mitochondrial proteins, i.e. voltage-dependent anion channel and/or uncoupling protein 2. These adaptations may increase the predisposal of these offspring to adult obesity. Increasing maternal nutrition in late gestation, however, can result in proportionately less fetal adipose tissue deposition in conjunction with enhanced abundance of uncoupling protein 1.