Changes In Maternal Metabolism Research Articles

Relation between abdominal subcutaneous fat tissue thickness and inflammatory markers during pregnancy.

IntroductionSubcutaneous abdominal fat thickness (SCFT) is important for predisposition to metabolic and cardiovascular diseases. Our aim was to evaluate maternal SCFT and metabolic changes (such as insulin resistance and high inflammatory markers) during pregnancy.Material and methodsA total of 92 pregnant women between 24–28 weeks of gestation were enrolled in the study. The SCFT was measured by ultrasonography and patients were divided into 2 groups according to thickness of maternal SCFT and body mass index (BMI). Groups were compared with each other for oral glucose loading test (OGL) results, and for haematological, biochemical and fetal biometric parameters.ResultsAfter analysis of frequency for SCFT, the most appropriate cut-off value for grouping patients was found to be 15 mm for SCFT. In 48 cases SCFT was over 15 mm. High C reactive protein (CRP) was found in 47.9% (23) of cases with SCFT over 15 mm. Serum haemoglobin A1c (HbA1c) level was significantly correlated with SCFT thickness. The most important factors for determination of OGL level were found to be serum HbA1c level, BMI and SCFT. In obese subjects (BMI ≥ 25 kg/m2), levels of inflammatory markers and SCFT thickness were higher. The CRP and γ-glutamyltransferase (GGT) levels were significantly correlated with BMI and SCFT.ConclusionsHigh SCFT during pregnancy is associated with elevated inflammatory marker levels and HbA1c. Pregnant women with thicker SCFT may be susceptible to the development of metabolic complications of pregnancy, such as gestational diabetes mellitus (GDM) and hypertension, as well as risk of future metabolic and cardiovascular disease.

Maternal Ileal Interposition Surgery Confers Metabolic Improvements to Offspring Independent of Effects on Maternal Body Weight in UCD-T2DM Rats

Increasing numbers of people are undergoing bariatric surgery, of which approximately half are women in their childbearing years. However, information on the long-term effects of maternal bariatric surgery in their children is lacking. Furthermore, since bariatric surgery is performed to reduce body weight, clinical studies have not been able to differentiate between benefits to the child due to maternal body weight loss versus other maternal postoperative metabolic changes. Therefore, we used the University of California, Davis, type 2 diabetes mellitus (UCD-T2DM) rat model to test the hypothesis that maternal ileal interposition (IT) surgery would confer beneficial metabolic effects in offspring, independent of effects on maternal body weight. IT surgery was performed on 2-month-old prediabetic female UCD-T2DM rats. Females were bred 3 weeks after surgery, and male pups were studied longitudinally. Maternal IT surgery resulted in decreased body weight in offspring compared with sham offspring (P < 0.05). IT offspring exhibited improvements of glucose-stimulated insulin secretion and nutrient-stimulated glucagon-like peptide-2 (GLP-2) secretion (P < 0.05). Fasting plasma unconjugated bile acid concentrations were 4-fold lower in IT offspring compared with sham offspring at two months of age (P < 0.001). Overall, maternal IT surgery confers modest improvements of body weight and improves insulin secretion and nutrient-stimulated GLP-2 secretion in offspring in the UCD-T2DM rat model of type 2 diabetes, indicating that this is a useful model for investigating the weight-independent metabolic effects of maternal bariatric surgery.

Insulin resistance and beta cell failure in late pregnant mares with a low body condition score

In pregnancy, changes in maternal metabolism are necessary to ensure normal development of the fetus. In pregnant mares, like many species, insulin mediated glucose uptake in maternal tissues is reduced (decreased insulin sensitivity), together with enhanced insulin secretion from pancreatic b cells (increased insulin responsiveness). Nevertheless the underlying mechanisms involved in these metabolic changes are not well defined. In examining such metabolic changes, we determined insulin and glucose responses in late pregnant mares with disparate body condition...

Maternal metabolic changes with dietary intake of blueberry during pregnancy and lactation predispose adult progeny to lower mammary tumor growth rate

We have shown the lower growth rates of tumors that developed from Wnt1‐transgenic (Tg) offspring of dams consuming whole blueberry powder (3% BB) during pregnancy and lactation, compared to those of control (Casein) dams. Dietary exposure at post‐weaning through lifetime did not mimic the effects of early BB exposure. The basis for maternal BB effects on mammary tumor growth was examined in dams exposed to BB or control diet as young adults (beginning at age 8 weeks) and throughout pregnancy and lactation. Dams at weaning were evaluated for growth and metabolic parameters. BB‐fed dams had lower abdominal and retroperitoneal fat pad weights than control‐fed dams, although their body weights did not differ. BB dams also displayed increased insulin sensitivity (lower blood glucose, serum insulin, HOMA) and higher serum glutathione and methionine levels. Isolated epithelial cells from pre‐neoplastic mammary tissues of Tg offspring exposed to maternal control and BB diets were analyzed for percentage of basal (CD29highCD24+) and luminal progenitor (CD29lowCD24+) populations. Maternal BB exposure (relative to control) resulted in lower percentage of the luminal subpopulation (6.4% vs 21%), which comprise the tumor bulk in Tg tissues. Results implicate the influence of the favorable metabolic and anti‐oxidative maternal environment with BB diet on developing mammary glands for the improved mammary tumor outcome.Grant Funding Source: USDA‐CRIS 6251–51000‐005–004S, Arkansas Biosciences Institute

Serum chemerin levels during normal human pregnancy

During gestation there are important changes in maternal metabolism and an increase in insulin resistance, coinciding with an increase in adiposity. Chemerin is an adipocytokine which is expressed and secreted in various tissues, including placenta, and may play an important role in metabolic regulation during pregnancy. The aim of this study was to determine serum levels of chemerin during gestation and compare them to other indicators of insulin resistance. A cross-sectional study was carried out analyzing serum chemerin levels of 20 pregnant women during three gestational periods, early, middle, and late (between the 10th and 14th, the 23rd and 26th, and the 34th and 37th week) and 20 non-pregnant women were used as a control group. An analysis of chemerin levels during the menstrual cycle was performed in an eumenorrheic group (n=16) in the early follicular (cycle day 4±1) and the midluteal phase (cycle day 22±1), demonstrating that serum chemerin levels did not fluctuate significantly. Serum levels of chemerin were significantly elevated during late gestation when compared to early (P<0.001) and middle (P=0.001) gestation and a negative correlation between serum chemerin and adiponectin levels (r=−0.1643) became more significant when the non-pregnant group was included in the calculations (r=−0.2471). There was no significant association of triglycerides, total cholesterol, LDL, HDL, insulin, and HOMA levels with chemerin. Although chemerin rose significantly and is negatively associated with adiponectin levels, it is not correlated with other markers of insulin sensitivity, suggesting that more study is needed to determine whether chemerin is useful in predicting insulin resistance during gestation.

Hypergravity disruption of homeorhetic adaptations to lactation in rat dams include changes in circadian clocks

SummaryAltered gravity load induced by spaceflight (microgravity) and centrifugation (hypergravity) is associated with changes in circadian, metabolic, and reproductive systems. Exposure to 2-g hypergravity (HG) during pregnancy and lactation decreased rate of mammary metabolic activity and increased pup mortality. We hypothesize HG disrupted maternal homeorhetic responses to pregnancy and lactation are due to changes in maternal metabolism, hormone concentrations, and maternal behavior related to gravity induced alterations in circadian clocks. Effect of HG exposure on mammary, liver and adipose tissue metabolism, plasma hormones and maternal behavior were analyzed in rat dams from mid-pregnancy (Gestational day [G]11) through early lactation (Postnatal day [P]3); comparisons were made across five time-points: G20, G21, P0 (labor and delivery), P1 and P3. Blood, mammary, liver, and adipose tissue were collected for analyzing plasma hormones, glucose oxidation to CO2 and incorporation into lipids, or gene expression. Maternal behavioral phenotyping was conducted using time-lapse videographic analyses. Dam and fetal-pup body mass were significantly reduced in HG in all age groups. HG did not affect labor and delivery; however, HG pups experienced a greater rate of mortality. PRL, corticosterone, and insulin levels and receptor genes were altered by HG. Mammary, liver and adipose tissue metabolism and expression of genes that regulate lipid metabolism were altered by HG exposure. Exposure to HG significantly changed expression of core clock genes in mammary and liver and circadian rhythms of maternal behavior. Gravity load alterations in dam's circadian system may have impacted homeorhetic adaptations needed for a successful lactation.

Maternal and fetal cord blood lipids in intrauterine growth restriction

Small for gestational age neonates (SGA) could be subdivided into two groups according to the underlying causes leading to low birth weight. Intrauterine growth restriction (IUGR) is a pathologic condition with diminished growth velocity and fetal compromised well-being, while non-growth restricted SGA neonates are constitutionally (genetically determined) small. Antenatal sonographic measurements are used to differentiate these two subgroups. Maternal metabolic changes contribute to the pathogenesis of IUGR. A disturbed lipid metabolism and cholesterol supply might affect the fetus, with consequences for fetal programming of cardiovascular diseases. We evaluated fetal serum lipids and hypothesized a more atherogenic lipoprotein profile in IUGR fetuses. Umbilical cord serum lipids and oxidative modified, low-density lipoprotein (oxLDL) concentrations were measured by colorimetric enzymatic measurements, or by ELISA. Values of IUGR (n=36) and constitutionally small for gestational age neonates (SGA, n=22) were compared with those of healthy, adequate for gestational age, born neonates (CN, n=97). SAS-statistic software was used and two-way ANOVA was adjusted for gestational age at delivery. Fetal high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC) concentrations were found to be lower in the IUGR compared to the CN and SGA groups (HDL-C: P<0.001, TC: P<0.01). Atherogenic indices, including the oxLDL/LDL-C ratio, were increased in the IUGR compared to the CN group (oxLDL/LDL-C ratio: P<0.001). Our results support the hypothesis of a disturbed cholesterol supply in IUGR fetuses. Born SGA has been shown to be a risk factor for developing cardiovascular disease later in life. Since HDL-C has anti-inflammatory properties, a reduced HDL-C during fetal development, and an increase in atherogenic indices, might provide a link to this observation in IUGR fetuses.

Changes in Maternal Glucose Metabolism after the Administration of Dexamethasone for Fetal Lung Development

Aims. Antenatal dexamethasone administration for fetal lung development may impair maternal glucose tolerance. In this study, we investigated whether glucose and insulin levels differed among singleton and twin pregnancies and pregnancies with impaired glucose tolerance (IGT) after treatment with dexamethasone. Methods. Singleton pregnancies, twin pregnancies, and pregnancies with IGT between 28 and 33 weeks of gestation whose mothers were treated with dexamethasone were enrolled in this study. Exclusion criteria included gestational hypertension, diabetes, renal disorders, and infectious diseases. The fasting plasma glucose and insulin levels were checked before administration and 24 h, 48 h, and 72 h after treatment was completed. Results. Mean glucose levels were significantly higher in the twin pregnancy and IGT groups at 24 h and 48 h after the administration of dexamethasone than those in the singleton pregnancy group (P < 0.05). Although there was no significant difference in glucose levels before administration and 72 h after dexamethasone administration among the three groups, insulin levels in the IGT group were significantly higher (P < 0.05). Insulin levels in the singleton pregnancy group at 24 h and 48 h after treatment were significantly lower than in the twin and IGT groups. Conclusion. The effects on maternal fasting blood glucose and insulin levels of dexamethasone administrated to promote fetal lung maturation correlated with embryo number and the presence of IGT.

Protein restriction in the pregnant mouse modifies fetal growth and pulmonary development: role of fetal exposure to β-hydroxybutyrate

Maternal undernutrition during sensitive periods of pregnancy results in offspring predisposed towards the development of a number of diseases of adulthood, including hypertension and diabetes. In order to determine the nature of any gross alterations in fetal growth during early organogenesis, we supplied timed-mated pregnant mice with diets containing 6% protein (6%P), 9% protein (9%P) or 18% protein (18%P; control) from day 0 of pregnancy. At embryonic days 11 (E11), 12 (E12) and 13 (E13), females were killed and fetuses removed. Gross morphological analysis revealed that fetal limb growth was impaired between E11 and E12 in 6%P animals, but this recovered by E13. Likewise, fetal liver growth and lung branching morphogenesis were seen to exhibit an initial growth impairment at E12 followed by a rapid recovery by E13. Coincident with the observed changes in fetal growth, we noted an elevation in maternal hepatic triglyceride content, expression of the ketogenic 3-hydroxy-3-methylglutaryl-CoA synthase 2 (Hmgcs2) and circulating plasma β-hydroxybutyrate (BOHB). In addition, fetal liver Hmgcs2 expression was switched on by E13 in both 6%P- and 9%P-exposed animals. Exogenous BOHB did not influence branching morphogenesis in fetal lung explant cultures; however, we cannot rule out the possibility that this may occur in vivo. In conclusion, we find that disturbance of fetal growth by maternal dietary protein restriction is associated and therefore potentially indicated by changes in maternal and fetal ketone body metabolism.

Zinc and reproduction: effects of zinc deficiency on prenatal and early postnatal development

A large body of evidence supports the concept that human pregnancy outcome is significantly influenced by the nutritional status of the mother. The consumption of "poor diets" has been associated with an increased risk for pregnancy complications, including gross structural birth defects, prematurity, low birth weight, and an increased risk for neurobehavioral and immunological abnormalities after birth. Forty-four years ago, zinc deficiency in mammals was shown to be teratogenic. Maternal zinc deficiency produces effects ranging from infertility and embryo/fetal death, to intrauterine growth retardation and teratogenesis. Postnatal complications of maternal zinc deficiency can also occur, and include behavioral abnormalities, impaired immunocompetence, and an elevated risk for high blood pressure in the offspring. It has been suggested that developmental zinc deficiency in humans can present a significant challenge to the conceptus, increasing the risk for numerous defects. Developmental zinc deficiency can occur through multiple pathways, and the concept that acute phase response-induced changes in maternal zinc metabolism may be a common cause of embryonic and fetal zinc deficiency is presented. Potential mechanisms underlying the teratogenic effects of zinc deficiency are reviewed. The potential value of maternal zinc supplementation in high risk pregnancies is discussed.

Maternal obesity and fetal metabolic programming: a fertile epigenetic soil

The incidence of obesity and overweight has reached epidemic levels in the United States and developed countries worldwide. Even more alarming is the increasing prevalence of metabolic diseases in younger children and adolescents. Infants born to obese, overweight, and diabetic mothers (even when normal weight) have increased adiposity and are at increased risk of later metabolic disease. In addition to maternal glucose, hyperlipidemia and inflammation may contribute to the childhood obesity epidemic through fetal metabolic programming, the mechanisms of which are not well understood. Pregravid obesity, when combined with normal changes in maternal metabolism, may magnify increases in inflammation and blood lipids, which can have profound effects on the developing embryo and the fetus in utero. Fetal exposure to excess blood lipids, particularly saturated fatty acids, can activate proinflammatory pathways, which could impact substrate metabolism and mitochondrial function, as well as stem cell fate, all of which affect organ development and the response to the postnatal environment. Fetal and neonatal life are characterized by tremendous plasticity and the ability to respond to environmental factors (nutrients, oxygen, hormones) by altering gene expression levels via epigenetic modifications. Given that lipids act as both transcriptional activators and signaling molecules, excess fetal lipid exposure may regulate genes involved in lipid sensing and metabolism through epigenetic mechanisms. Epigenetic regulation of gene expression is characterized by covalent modifications to DNA and chromatin that alter gene expression independent of gene sequence. Epigenetic modifications can be maintained through positive and negative feedback loops, thereby creating stable changes in the expression of metabolic genes and their main transcriptional regulators. The purpose of this article is to review current literature on maternal-fetal lipid metabolism and maternal obesity outcomes and to suggest some potential mechanisms for fetal metabolic programming in key organ systems that regulate postnatal energy balance, with an emphasis on epigenetics and the intrauterine environment.

Fatty Acid Supply to the Human Fetus

Deposition of fat in the fetus increases exponentially with gestational age, reaching its maximal rate-around 7 g/day or 90% of energy deposition-at term. In late pregnancy, many women consuming contemporary Western diets may not be able to meet the fetal demand for n-3 long chain polyunsaturated fatty acids (LCPUFAs) from the diet alone. Numerous mechanisms have evolved to protect human offspring from extreme variation or deficiency in the maternal diet during pregnancy. Maternal adipose tissue is an important source of LCPUFA. Temporal changes in placental function are synchronized with maternal metabolic and physiological changes to ensure a continuous supply of n-3 and n-6 LCPUFA-enriched fat to the fetus. LCPUFA storage in fetal adipose tissue provides an important source of LCPUFA during the critical first months of postnatal life. An appreciation of these adaptations is important in any nutritional strategy designed to improve the availability of fatty acids to the fetus.

Serotonin regulates pancreatic beta cell mass during pregnancy

During pregnancy, the energy requirements of the fetus impose changes in maternal metabolism. Increasing insulin resistance in the mother maintains nutrient flow to the growing fetus, while prolactin and placental lactogen counterbalance this resistance and prevent maternal hyperglycemia by driving expansion of the maternal population of insulin-producing β-cells1–3. However, the exact mechanisms by which the lactogenic hormones drive β-cell expansion remain uncertain. Here we show that serotonin acts downstream of lactogen signaling to drive β-cell proliferation. Serotonin synthetic enzyme Tph1 and serotonin production increased sharply in β-cells during pregnancy or after treatment with lactogens in vitro. Inhibition of serotonin synthesis by dietary tryptophan restriction or Tph inhibition blocked β-cell expansion and induced glucose intolerance in pregnant mice without affecting insulin sensitivity. Expression of the Gαq-linked serotonin receptor Htr2b in maternal islets increased during pregnancy and normalized just prior to parturition, while expression of the Gαi-linked receptor Htr1d increased at the end of pregnancy and postpartum. Blocking Htr2b signaling in pregnant mice also blocked β-cell expansion and caused glucose intolerance. These studies reveal an integrated signaling pathway linking β-cell mass to anticipated insulin need during pregnancy. Modulators of this pathway, including medications and diet, may affect the risk of gestational diabetes4.

Changes in fetal myocardial glycogen during hypoxia induced by maternal acute hemorrhagic shock.

Fetal and maternal metabolic and hemodynamic changes, with special reference to fetal myocardial glycogen, were investigated during hypoxia induced by maternal acute hemorrhage. Myocardial glycogen gradually decreased during the hypotensive period to nearly half the initial control value. Linear relationships were observed between miocardial glycogen and fetal pH and fetal heart rate. The role of myocardial glycogen in cardiac function and its metabolic changes during hyposica were evaluated.

Prepartum dietary energy source fed to beef cows: I. Effects on pre- and postpartum cow performance1

Mature Angus-cross beef cows (n = 144) were used to determine effects of late gestation dietary energy source on pre- and postpartum cow performance in a complete randomized block design experiment. Cows were adapted to diets starting at 167 +/- 9 d of gestation and fed until 1 wk before expected calving date. Cows were fed 1 of 3 dietary energy sources: grass hay (HY), corn (CN), or dried distillers grains (DDGS). Cows allotted to HY were allowed ad libitum access to round-bale grass hay, and average hay disappearance was 12.4 kg/d. Limit-fed corn and DDGS diets contained 5.3 kg of whole-shelled corn or 4.1 kg of DDGS, respectively, plus 2.1 kg of hay, and 1.0 kg of supplement to meet cow nutritional needs during late gestation and to allow for an energy intake similar to HY. Every 21 d, BW, BCS, and ultrasound measurement of backfat between the 12th and 13th ribs were collected. At 210 d in gestation, jugular blood samples were collected from cows at 0, 3, 6, and 9 h postfeeding and were analyzed for glucose, insulin, NEFA, and blood urea N (BUN) concentrations. After parturition, cows were fed a common diet and managed similarly. Milk production was determined by weigh-suckle-weigh procedure on d 31, 100, and 176 postpartum. Cows fed DDGS during late gestation gained more (P = 0.04) BW than cows fed HY or CN; however, no difference in BCS change was detected (P = 0.28) among treatments. Plasma glucose concentrations were similar among treatments (P = 0.64), whereas insulin concentrations at 3 h postfeeding were greater (P = 0.002) for cows fed DDGS than those fed HY or CN. Plasma BUN concentrations were greater (P < or = 0.02) for cows fed DDGS vs. CN or HY up to 6 h postfeeding. Birth weight was greater (P < 0.001) for calves from cows fed CN and DDGS than for those fed HY, but this did not result in any differences in frequency of dystocia (P = 0.21). Prepartum energy source did not affect conception rates (P = 0.79), milk production (P > or = 0.51), or milk composition (P > or = 0.39). Maternal dietary energy source in late gestation did not affect pre- or postpartum cow performance, but did change plasma hormones and metabolites during gestation. Heavier birth weights in calves from cows fed CN or DDGS indicate the changes in maternal metabolism affected energy partitioning of nutrients to the fetus and subsequent fetal growth.

A HIGH FRUCTOSE DIET AFFECTS SYNTHESIS AND COMPOSITION OF FATTY ACIDS IN THE LIVER OF LACTATING DAMS AND BODY OF THEIR SUCKLING PUPS

Fructose (F) is a potent stimulator of hepatic lipogenesis. Long chain polyunsaturated fatty acids (LC‐PUFAs) are required during pregnancy and lactation for normal fetal and neonatal development. Despite numerous studies on F‐induced metabolic disorders in adults, the effects of dietary F on maternal and fetal lipid metabolism have not been studied. To evaluate the effects of excessive F consumption on FA synthesis, 3 groups of pregnant rats were fed isocaloric, isolipidic 60% glucose, F or starch diets from d2 of gestation to end of lactation. Compared to lactating dams fed glucose and starch, dams fed F had a 2X increase in liver mass and 4–10X increases in lipid, saturated FA, and monounsaturated FA (MUFA) content because of a dramatic rise in C16:0 and C18:1n‐9 levels. Whole body adiposity of dams was similar. Despite small increases in PUFA n‐6 and n‐3 precursors in the liver of F fed dams, C22:6n‐3 abundance was lower, suggesting that F impairs LC‐PUFA synthesis. At birth, body adiposity and fatty acid composition of pups were independent of the maternal diet. At 10 and 21 d old, % MUFA was higher in pups from F‐fed dams. During gestation, selective placental transfer of FA may shield the fetus from changes in maternal FA metabolism. After birth, the high F diet which dramatically alters maternal lipid metabolism can also alter the FA composition of the offspring, probably through FA composition in milk. (NIH‐RDK075617)

Diabetic parturient - Anaesthetic implications

Pregnancy induces progressive changes in maternal carbohydrate metabolism. As pregnancy advances insulin resistance and diabetogenic stress due to placental hormones necessitate compensatory increase in insulin secretion. When this compensation is inadequate gestational diabetes develops. ‘Gestational diabetes mellitus’ (GDM) is defined as carbohydrate intolerance with onset or recognition during pregnancy. Women diagnosed to have GDM are at increased risk of future diabetes predominantly type 2 DM as are their children. Thus GDM offers an important opportunity for the development, testing and implementation of clinical strategies for diabetes prevention. Timely action taken now in screening all pregnant women for glucose intolerance, achieving euglycaemia in them and ensuring adequate nutrition may prevent in all probability, the vicious cycle of transmitting glucose intolerance from one generation to another. Given that diabetic mothers have proportionately larger babies it is likely that vaginal delivery will be more difficult than in the normal population, with a higher rate of instrumentally assisted delivery, episiotomy and conversion to urgent caesarean section. So an indwelling epidural catheter is a better choice for labour analgesia as well to use, should a caesarean delivery become necessary. Diabetes in pregnancy has potential serious adverse effects for both the mother and the neonate. Standardized multidisciplinary care including anaesthetists should be carried out obsessively throughout pregnancy. Diabetes is the most common endocrine disorder of pregnancy. In pregnancy, it has considerable cost and care demands and is associated with increased risks to the health of the mother and the outcome of the pregnancy. However, with careful and appropriate screening, multidisciplinary management and a motivated patient these risks can be minimized.

Protein restriction during pregnancy affects maternal liver lipid metabolism and fetal brain lipid composition in the rat

Suboptimal developmental environments program offspring to lifelong metabolic problems. The aim of this study was to determine the impact of protein restriction in pregnancy on maternal liver lipid metabolism at 19 days of gestation (dG) and its effect on fetal brain development. Control (C) and restricted (R) mothers were fed with isocaloric diets containing 20 and 10% of casein. At 19 dG, maternal blood and livers and fetal livers and brains were collected. Serum insulin and leptin levels were determinate in mothers. Maternal and fetal liver lipid and fetal brain lipid quantification were performed. Maternal liver and fetal brain fatty acids were quantified by gas chromatography. In mothers, liver desaturase and elongase mRNAs were measured by RT-PCR. Maternal body and liver weights were similar in both groups. However, fat body composition, including liver lipids, was lower in R mothers. A higher fasting insulin at 19 dG in the R group was observed (C = 0.2 +/- 0.04 vs. R = 0.9 +/- 0.16 ng/ml, P < 0.01) and was inversely related to early growth retardation. Serum leptin in R mothers was significantly higher than that observed in C rats (C = 5 +/- 0.1 vs. R = 7 +/- 0.7 ng/ml, P < 0.05). In addition, protein restriction significantly reduced gene expression in maternal liver of desaturases and elongases and the concentration of arachidonic (AA) and docosahexanoic (DHA) acids. In fetus from R mothers, a low body weight (C = 3 +/- 0.3 vs. R = 2 +/- 0.1 g, P < 0.05), as well as liver and brain lipids, including the content of DHA in the brain, was reduced. This study showed that protein restriction during pregnancy may negatively impact normal fetal brain development by changes in maternal lipid metabolism.

The prolonged effect of repeated maternal glucocorticoid exposure on the maternal and fetal leptin/insulin-like growth factor axis in Papio species.

Maternal obesity represents a risk factor for pregnancy-related complications. Glucocorticoids are known to promote obesity in adults. We evaluated maternal and fetal metabolic changes during and after 3 weekly courses of betamethasone administered to pregnant baboons (Papio subspecies) at doses equivalent to those given to pregnant women. Betamethasone administration during the second half of pregnancy increased maternal weight but neither maternal food intake nor fetal weight, as assessed at the end of gestation. Betamethasone increased maternal serum glucose concentration, the ratio of insulin-like growth factor-I and insulin-like growth factor binding protein-3, and serum leptin during treatment (normalized by 17, 35, and 45 days posttreatment, respectively, for each parameter). Maternal and fetal serum leptin concentrations did not differ between groups at the end of gestation. Prolonged maternal hyperleptinemia caused by betamethasone administration in the second half of gestation did not change fetal metabolic parameters measured and placental leptin distribution at the end of gestation.

Lipoprotein metabolism and vascular complications in pregnancy

Human pregnancy is characterized by striking changes in maternal metabolism and body composition in order to provide sufficient energy and nutrients to the developing fetus. There are marked increases in plasma lipid concentrations as gestation advances, with plasma cholesterol and triglyceride concentrations rising typically by 25–50% and 200–400%, respectively. These changes are due to the combined effect of increased adipose tissue lipolysis in late pregnancy and maternal hormonal changes. Essential fatty acids and cholesterol are transported to the fetus via the placenta. In women with additional metabolic stress, such as those with gestational diabetes mellitus and obesity, there are alterations in lipid and lipoprotein metabolism consistent with increased insulin resistance. In pre-eclampsia, there is an exaggerated early rise in plasma triglycerides and free fatty acid concentrations in combination with an increase in the proportion of small dense LDL and a lesser rise in HDL-C, changes that may co...