Metabolic Biomarkers in Adults with Type 2 Diabetes: The Role of PPAR-γ2 and PPAR-ß/δ Polymorphisms.

Glucose and lipid metabolism regulation by the peroxisome proliferator-activated receptors (PPARs) has been extensively reported. However, the role of their polymorphisms remains unclear. OBJECTIVE: To determine the relation between PPAR-γ2 rs1801282 (Pro12Ala) and PPAR-ß/δ rs2016520 (+294T/C) polymorphisms and metabolic biomarkers in adults with type 2 diabetes (T2D). MATERIALS AND METHODS: We included 314 patients with T2D. Information on anthropometric, fasting plasma glucose (FPG), HbA1c and lipid profile measurements was taken from clinical records. Genomic DNA was obtained from peripheral blood. End-point PCR was used for PPAR-γ2 rs1801282, while for PPAR-ß/δ rs2016520 the PCR product was digested with Bsl-I enzyme. Data were compared with parametric or non-parametric tests. Multivariate models were used to adjust for covariates and interaction effects. RESULTS: minor allele frequency was 12.42% for PPAR-γ2 rs1801282-G and 13.85% for PPAR-ß/δ rs2016520-C. Both polymorphisms were related to waist circumference; they showed independent effects on HbA1c, while they interacted for FPG; carriers of both PPAR minor alleles had the highest values. Interactions between FPG and polymorphisms were identified in their relation to triglyceride level. CONCLUSIONS: PPAR-γ2 rs1801282 and PPAR-ß/δ rs2016520 polymorphisms are associated with anthropometric, glucose, and lipid metabolism biomarkers in T2D patients. Further research is required on the molecular mechanisms involved.

Neural crest derivatives and neuroendocrine cells in the gut of anencephalic and fetuses without congenital defects.

BACKGROUND: The enteric nervous system (ENS), a component of the peripheral nervous system in the intestinal walls, regulates motility, secretion, absorption, and blood flow. Neural crest (NC) migration, fundamental for ENS development, may be altered by central nervous system development alterations, such as neural tube defects (NTD). Intestinal innervation anomalies have been correlated to NTD. We aim to describe the ENS on a fetus with NTD and fetuses without congenital defects (FWCD). CASES: Two male and four female FWCD, 18-20 weeks-gestation (WG), and a 25 WG female anencephalic fetus. Samples from the pancreatoduodenal groove, jejunum, cecum, rectum, and appendix were analyzed by immunohistochemistry. Nervous plexuses were marked with Neuron-specific enolase and S-100; enteric glial cells with CD56; neuroendocrine cells with chromogranin and synaptophysin, and interstitial cells of Cajal (ICC) with CD117. RESULTS AND CONCLUSION: The anencephalic fetus presented a rudimentary brainstem with a cerebellum. Partial frontal, temporal, and occipital bones were found. A large atrial septal defect, an enlarged kidney with a duplex collecting system and a single adrenal gland were found. NSE, S100, and CD56, showed the presence of the myenteric and submucous plexuses of the ENS; scarce interplexus reactivity may indicate inadequate development. Pancreatic and gut neuroendocrine cells, identified with chromogranin and CD56, showed that the enteroendocrine system is present. Findings on FWCD using these markers are consistent with literature descriptions. Vagal NC migration appears to be unaffected despite the presence of anencephaly, although maturation of the ENS may be altered.

Pro12Ala PPAR-γ2 and +294T/C PPAR-δ Polymorphisms and Association with Metabolic Traits in Teenagers from Northern Mexico.

Peroxisome proliferator-activated receptors (PPARs) play roles in glucose and lipid metabolism regulation. Pro12Ala PPAR-γ2 and +294T/C PPAR-δ have been associated with dyslipidemia, hyperglycemia and high body mass index (BMI). We compared metabolic traits and determined associations with Pro12Ala PPAR-γ2 or +294T/C PPAR-δ polymorphism among teenagers from different ethnicity. Four hundred and twelve samples with previous biochemical and biometric measurements were used. Genomic DNA from peripheral blood was extracted and analyzed by end-point PCR for Pro12Ala PPAR-γ2. The +294T/C PPAR-δ PCR product was also digested with Bsl I. Two genotype groups were formed: major allele homozygous and minor allele carriers. Pro12Ala PPAR-γ2 G minor allele frequencies were: 10% in Mestizo-1, 19% in Mestizo-2, 23% in Tarahumara, 12% in Mennonite, and 17% in the total studied population. The +294T/C PPAR-δ C minor allele frequencies were: 18% in Mestizo-1, 20% in Mestizo-2, 6% in Tarahumara, 13% in Mennonite, and 12% in the total studied population. Teenagers with PPAR-γ2 G allele showed a greater risk for either high waist/height ratio or low high-density lipoprotein; and, also had lower total cholesterol. Whereas, PPAR-γ2 G allele showed lower overweight/obesity phenotype (BMI Z-score) frequency, PPAR-δ C allele was a risk factor for it. Metabolic traits were associated with both PPAR polymorphisms.

Assessment of Physical Activity in Adults: A Review of Validated Questionnaires From a Nutritionist's Point of View.

Physical activity (PA) is a component of total energy expenditure. PA and PA energy expenditure (PAEE) can be estimated by objective techniques (OTs). However, the use of questionnaires is frequent in clinical settings and epidemiological studies. We conducted a search on PubMed, Scopus, and Google Scholar databases to perform a review of studies reporting the reliability and validity of PA questionnaires validated against OTs-doubly labeled water (DLW) or accelerometers-in free-living adults. We selected original articles published between 2009 and 2019 that reported validation studies of PA questionnaires. We identified 53 studies that fulfilled the eligibility criteria. Four PA questionnaires were validated against DLW and the remaining against accelerometers. Three questionnaires were compared with both DLW and accelerometer results. The correlation between questionnaire-estimated PAEE and DLW results ranged from r = .22 to r = .46, while that between questionnaire-estimated total PA (TPA) and accelerometer results ranged from r = .11 to r = .54 The intraclass correlation coefficients were between .56 and .84. Despite having good reliability, most of the questionnaires included in this review have shown limited validity for estimating TPA in adults. OTs should be considered as a first option, when possible. Further research is warranted on techniques to obtain more accurate PA and PAEE estimates.

Relation between pregestational obesity and characteristics of the placenta.

Objective: To evaluate the morphology of the placenta in patients with pregestational overweight (OW), pregestational obesity (PGOB), or normal weight.Methods: A cross-sectional study including women (n = 114) ≥20 years of age with a singleton pregnancy was carried out. The groups were integrated according to pregestational body mass index (BMI): 51 patients had a normal BMI (18.5-24.99 kg/m2), 30 were overweight (25-29.99 kg/m2), and 33 women were obese (≥30.0 kg/m2). A morphometric study of the placenta was performed and the placental maturity index (PMI) was calculated according to the formula: PMI = number of vasculo-syncytial membranes (VSM) in 1 mm2/VSM thickness. In the histopathological study, the presence of infarcts, calcifications, hemorrhage, thrombosis, fibrosis, cysts, and edema was determined.Results: The weight and length of newborns at birth were greater in the group with PGOB (p < .01). We observed a lower number of VSM (29 ± 9 versus 39 ± 13 and 34 ± 11) and a greater thickness (1.05 ± 0.24 versus 0.95 ± 0.08 and 0.89 ± 0.09) and, therefore, a lower PMI (29.75 ± 12.63 versus 40.88 ± 15.25 and 39.28 ± 14.4) in the group of women with PGOB compared with the group of women with OW or normal weight (p < .01). The histopathological analyses showed a greater frequency of edema and cysts in the PGOB group.Conclusion: PGOB is associated with a higher placental weight and newborn weight, a lower PMI, and the presence of histopathological alterations. The preceding points highlight the importance of promoting an appropriate pregestational weight in women of reproductive age.

Prepregnancy Obesity, Maternal Dietary Intake, and Oxidative Stress Biomarkers in the Fetomaternal Unit.

BACKGROUND: Obesity and pregnancy increase levels of maternal oxidative stress (OS). However, little is known about the maternal, placental, and neonatal OS status. OBJECTIVE: To analyze the relation between prepregnancy obesity and the expression of OS markers and antioxidant capacity in the fetomaternal unit and their association with dietary intake. METHODS: This cross-sectional study included 33 women with singleton, noncomplicated pregnancies. Two groups were formed: women with prepregnancy body mass index (pBMI) within normal range (18.5-24.9 kg/m2, n = 18) and women with pBMI ≥ 30 kg/m2, suggestive of obesity (n = 15). Dietary and clinical information was obtained by questionnaire and from clinical records. Total antioxidant capacity (TAC) and malondialdehyde (MDA) concentration were measured on maternal and cord serum by colorimetric techniques, and placental expression of glutathione peroxidase 4 (GPx4) was measured by immunohistochemistry. RESULTS: Placental GPx4 expression was lower in the group with pBMI suggestive of obesity than in the normal weight group (ß = -0.08, p = 0.03, adjusted for gestational age and magnesium intake). Concentrations of TAC and MDA in maternal and cord blood were not statistically different between groups (p>0.05). Cord MDA concentration was related to maternal MDA concentration (ß = 0.40, p < 0.01), vitamin A intake (tertile 2: ß = -0.04, p = 0.40, tertile 3: ß = 0.13, p = 0.03, vs tertile 1), and placental GPx4 expression (ß = -0.09, p = 0.02). CONCLUSION: Prepregnancy obesity is associated with a decrease in GPx4 expression in the placenta, which is related to OS in the newborn. The influence of micronutrient intake on OS biomarkers highlights the importance of nutritional assessment during pregnancy and adequate prenatal care.

Holoprosencefalia semilobar y malformaciones asociadas: reporte de caso y algunas consideraciones / Semilobar holoprosencephaly and associated malformations: case report and some considerations

RESUMEN: El defecto más común del prosencéfalo es la holoprosencefalia (HPE), caracterizada por ausencia en la división del prosencéfalo. La holoprosencefalia tiene una prevalencia de 1/10.000 en recién nacidos; la ciclopía de 1/100.000 nacidos y la agnatia asociada a holoprosencefalia de 0,8 a 10 %. El objetivo fue describir las características morfológicas e histopatológicas de un feto humano con holoprosencefalia y sus malformaciones asociadas. Se estudió un feto masculino. Se le realizó microdisección bajo el estereomicroscopio, toma de microfotografías con cámara AxioCam y software AxioVision 4.8, y estudio histopatológico. La edad gestacional estimada fue de 12,4-13,2 semanas, encontrándose como hallazgos la HPE semilobar asociada a ciclopía, esbozo oral hipoplásico sin apertura oral, cubierta por una membrana y ausencia de labios. El estudio histopatológico reportó: ojo con lente, retina y córnea únicos; en la cara, probóscide con cartílago tubular en formación asociado a mesénquima y cubierta muscular esquelética, y cavidad oral pequeña, circunscrita por mandíbula hipoplásica conformada por cartílago. Se revisa la literatura y se reafirma la necesidad de estudio multidisciplinario de esta patología para mejorar su comprensión.

SUMMARY: The most common defect of the forebrain is holoprosencephaly (HPE), characterized by absence in the forebrain division. Holoprosencephaly has a prevalence of 1 / 10,000 in newborns; the cyclopia of 1 / 100,000 births and the agnathia, in a series of cases of holoprosencephaly ranges from 0.8 to 10 %. The objective was the description of the morphological and histopathological characteristics of fetus with holoprosencephaly and its associated malformations. A male fetus was studied. Microdissection was performed under the stereomicroscope, taking microphotographs with AxioCam camera and AxioVision 4.8 software, and histopathological study. The estimated gestational age was 12.4-13.2 weeks, the findings were semilobar HPE, associated with cyclopia, hypoplastic oral outline without buccal opening, covered by a membrane and lips absence. The histopathological study reported: eye with lens, retina and cornea only; in the face, proboscis with tubular cartilage in formation associated with mesenchyme and musculoskeletal sheath, and small oral cavity, delimited by hypoplastic mandible conformed by cartilage. The literature is reviewed and reaffirmed the need for multidisciplinary studies of this disease to improve their understanding.

Folate transporter expression in placenta from pregnancies complicated with birth defects.

BACKGROUND: Folate plays a fundamental role for fetal development, participating in cell division, embryogenesis, and fetal growth. The fetus depends on maternal supply of folate across the placenta. The objective of this study was to compare the expression of Folate Receptor-α (FR-α), Reduced Folate Carrier (RFC), and Proton Coupled Folate Transporter (PCFT) in placentas from pregnancies complicated with birth defects (BD) and controls. METHODS: Case-control study, including placentas of BD-complicated pregnancies (n = 25) and a control group (n = 25). We determined the placental expression of FR-α, RFC, and PCFT by immunohistochemistry. Optical density was measured to obtain a relative quantification of the expression. RESULTS: The expression of PCFT was greater in placentas from pregnancies complicated with BD than in those from the control group (p < .01). The expression of FR-α and RFC was not different between groups. CONCLUSION: The expression of PCFT in placentas from BD-complicated pregnancies is increased, possibly as an adaptive response to increase the folate flux at the maternal-fetal interface.

Maternal and postweaning folic acid supplementation interact to influence body weight, insulin resistance, and food intake regulatory gene expression in rat offspring in a sex-specific manner.

Maternal intake of multivitamins or folic acid above the basal dietary requirement alters the growth and metabolic trajectory of rat offspring. We hypothesized that a modest increase in the folic acid content of maternal diets would alter the offspring's metabolic phenotype, and that these effects could be corrected by matching the folic acid content of the offspring's diet with that of the maternal diet. Female Sprague-Dawley rats were placed on a control or a 2.5× folic acid-supplemented diet prior to mating and during pregnancy and lactation. At weaning, pups from each maternal diet group were randomized to the control or to the 2.5× folic acid-supplemented diet for 25 weeks. Male pups from dams fed the folic acid-supplemented diet were 3.7% heavier than those from control-fed dams and had lower mRNA expression for leptin receptor Obrb isoform (Lepr) (11%) and Agouti-related protein (Agrp) (14%). In contrast, female pups from folic acid-supplemented dams were 5% lighter than those from control-fed dams and had lower proopiomelanocortin (Pomc) (42%), Lepr (32%), and Agrp (13%), but higher neuropeptide Y (Npy) (18%) mRNA expression. Folic acid supplementation ameliorated the alterations induced by maternal folic acid supplementation in male pups and led to the lowest insulin resistance, but the effects were smaller in female pups and led to the highest insulin resistance. In conclusion, maternal folic acid supplementation at 2.5× the control level was associated with alterations in body weight and hypothalamic gene expression in rat offspring in a sex-specific manner, and some of these effects were attenuated by postweaning folic acid supplementation.

High vitamin A intake during pregnancy modifies dopaminergic reward system and decreases preference for sucrose in Wistar rat offspring.

High multivitamin (HV) content in gestational diets has long-term metabolic effects in rat offspring. These changes are associated with in utero modifications of gene expression in hypothalamic food intake regulation. However, the role of fat-soluble vitamins in mediating these effects has not been explored. Vitamin A is a plausible candidate due to its role in gene methylation. Vitamin A intake above requirements during pregnancy affects the development of neurocircuitries involved in food intake and reward regulation. Pregnant Wistar rats were fed AIN-93G diets with the following content: recommended multivitamins (1-fold multivitamins: RV), high vitamin A (10-fold vitamin A: HA) or HV with only recommended vitamin A (10-fold multivitamins, 1-fold vitamin A: HVRA). Body weight, food intake and preference, mRNA expression and DNA methylation of hippocampal dopamine-related genes were assessed in male offspring brains at different developmental windows: birth, weaning and 14weeks postweaning. HA offspring had changes in dopamine-related gene expression at all developmental windows and DNA hypermethylation in the dopamine receptor 2 promoter region compared to RV offspring. Furthermore, HA diet lowered sucrose preference but had no effect on body weight and expression of hypothalamic genes. In contrast, HVRA offspring showed only at adulthood changes in expression of hippocampal genes and a modest effect on hypothalamic genes. High vitamin A intake alone in gestational diets has long-lasting programming effects on the dopaminergic system that are further translated into decreased sucrose preference but not food intake.

Maternal and Perinatal Outcomes Among Adolescents and Mature Women: A Hospital-Based Study in the North of Mexico.

STUDY OBJECTIVE: To compare maternal and newborn pregnancy outcomes from adolescents and mature women. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study was carried out in a public hospital, including women with singleton pregnancies, who were classified according to their age, as follows: group 1: younger than 16 years old (n = 37), group 2: 16-19 years old (n = 288), and group 3: 20-34 years old (n = 632). INTERVENTIONS AND MAIN OUTCOME MEASURES: Information on clinical characteristics, gynecological and obstetric history, pregnancy complications, and perinatal outcomes was obtained through interviews and from clinical records. RESULTS: Thirty-four percent of deliveries were from adolescents. Mature women were more likely to have prepregnancy overweight or obesity than adolescents (odds ratio [OR] = 2.4, 95% confidence interval [CI], 1.7-3.4). The frequency of maternal complications during pregnancy or delivery was not different between groups. Birth asphyxia was more frequent in group 2 (P = .02). Women with inadequate prenatal care had an increased risk of preterm deliveries (OR = 1.64; 95% CI, 1.06-2.54) and of having newborns with low birth weight (OR = 2.02; 95% CI, 1.22-3.35). Weight of newborns from noncomplicated pregnancies was lower in group 1 (P = .02), after adjustment for prepregnancy body mass index, gestational weight gain, preterm delivery, and newborn sex. CONCLUSION: The frequency of maternal and perinatal complications was similar in adolescents and mature women. Birth weight was decreased in noncomplicated pregnancies of adolescents younger than 16 years of age. Adequate prenatal care might be helpful in prevention of some adverse perinatal outcomes.

Body composition and newborn birthweight in pregnancies of adolescent and mature women.

Teenage pregnancy has been associated with adverse effects for the mother and the newborn (NB). In order to compare body composition (BC) between adolescents (Ad) and mature women (MW) during pregnancy and to determine the difference in birthweight and perinatal morbidity, pregnant Ad (n=40) and MW (n=227) were studied. BC changes between the second and third trimesters were determined by multifrequency bioelectrical impedance analysis, and birthweight and NB morbidity were evaluated. During the second and third trimesters of the pregnancy, fat mass was lower in the Ad group [16 kg (13-19)] than in the MW group [22 kg (17-27)] (P<0.01; median and quartiles 1-3). Fat-free mass increased by 3.09 kg (2.29-4.20) and 2.20 kg (1.0-3.59) (P≤0.01), and total body water increased by 2.77 L (0.84-4.49) vs. 2.04 L (0.55-3.89) (P=0.36), in the Ad and MW groups, respectively (median and quartiles 1-3). Birthweight was not significantly different between NBs of Ad (3223 ± 399 g) and NBs of MW (3312 ± 427 g, P=0.22). The youngest Ad (<18 year old, n=8) had NB with lower birthweight than MW (3031 ± 503 g, P=0.06). NBs of Ad mothers showed a non-significant trend towards a higher rate of morbidity relative to the NBs of MW. In conclusion, the BC of Ad differs from that of MW during pregnancy. In addition, the NB infants of Ad mothers tended to have a lower birthweight than those from MW, a result that suggests that the Ad should be in strict prenatal control.

Increasing vitamin A in post-weaning diets reduces food intake and body weight and modifies gene expression in brains of male rats born to dams fed a high multivitamin diet.

High multivitamin gestational diets (HV, 10-fold AIN-93G levels) increase body weight (BW) and food intake (FI) in rat offspring weaned to a recommended multivitamin (RV), but not to a HV diet. We hypothesized that high vitamin A (HA) alone, similar to HV, in post-weaning diets would prevent these effects of the HV maternal diet consistent with gene expression in FI and reward pathways. Male offspring from dams fed HV diets were weaned to a high vitamin A (HA, 10-fold AIN-93G levels), HV or RV diet for 29 weeks. BW, FI, expression of genes involved in regulation of FI and reward and global and gene-specific DNA methylation of pro-opiomelanocortin (POMC) in the hypothalamus were measured. Both HV and HA diets slowed post-weaning weight gain and modified gene expression in offspring compared to offspring fed an RV post-weaning diet. Hypothalamic POMC expression in HA offspring was not different from either HV or RV, and dopamine receptor 1 was 30% (P<.05) higher in HA vs. HV, but not different from RV group. Hippocampal expression of serotonin receptor 1A (40%, P<.01), dopamine receptor 2 (40%, P<.05) and dopamine receptor 5 (70%, P<.0001) was greater in HA vs. RV fed pups and is 40% (P<.01), 50% (P<.05) and 40% (P<.0001) in HA vs. HV pups, respectively. POMC DNA methylation was lower in HA vs. RV offspring (P<.05). We conclude that high vitamin A in post-weaning diets reduces post-weaning weight gain and FI and modifies gene expression in FI and reward pathways.

Placental maturity, hypertensive disorders of pregnancy and birth weight.

OBJECTIVES: To compare maturity of placentas from women with hypertensive disorders with those from normotensive pregnancies and to determine the relationship between placental maturity (PM) and the diagnosis of small-for-gestational-age (SGA) in the newborns. MATERIALS AND METHODS: We examined placental stained specimens from women with normotensive pregnancies (n = 100), diagnosis of gestational hypertension (n = 38), mild (n = 10), or severe preeclampsia (n = 34) in an optical microscope. Placental Maturity Index (PMI) was calculated as the number of vasculo-syncytial membranes (VSM) in 1 mm(2) divided by VSM thickness (µm). Hypermaturity was defined as >90th percentile of the PMI from placentas of normotensive pregnancies. Newborns were classified as SGA, adequate-for-gestational-age (AGA) or large-for-gestational-age (<10th, 10-90th, and >90th percentile from weight for gestational age reference tables, respectively). RESULTS: PMI in preeclamptic women (taking together mild and severe preeclampsia, PMI = 43.4 ± 1.6) was significantly higher than in normotensive women (PMI = 36 ± 2, p = 0.045). Hypermaturity was more frequent (p < 0.05) in placentas from women with preeclampsia than in those from normotensive women only in preterm pregnancies (<37 weeks), but not in those at term (p = 0.41). The frequency of hypermaturity in placentas from women with gestational hypertension was not statistically different than in normotensive women. Hypermaturity was also more frequent in placentas from SGA (OR = 2.63, p < 0.05) than in AGA newborns. CONCLUSION: The PMI was increased in preeclampsia, but not in gestational hypertension. Placental hypermaturity was also associated with the diagnosis of SGA in newborns. PM might have a role in the relationship between maternal factors and SGA.

High Folic Acid Intake during Pregnancy Lowers Body Weight and Reduces Femoral Area and Strength in Female Rat Offspring.

Rats fed gestational diets high in multivitamin or folate produce offspring of altered phenotypes. We hypothesized that female rat offspring born to dams fed a gestational diet high in folic acid (HFol) have compromised bone health and that feeding the offspring the same HFol diet attenuates these effects. Pregnant rats were fed diets with either recommended folic acid (RFol) or 10-fold higher folic acid (HFol) amounts. Female offspring were weaned to either the RFol or HFol diet for 17 weeks. HFol maternal diet resulted in lower offspring body weights (6%, P = 0.03) and, after adjusting for body weight and femoral length, smaller femoral area (2%, P = 0.03), compared to control diet. After adjustments, HFol pup diet resulted in lower mineral content (7%, P = 0.01) and density (4%, P = 0.002) of lumbar vertebra 4 without differences in strength. An interaction between folate content of the dam and pup diets revealed that a mismatch resulted in lower femoral peak load strength (P = 0.01) and stiffness (P = 0.002). However, the match in folate content failed to prevent lower weight gain. In conclusion, HFol diets fed to rat dams and their offspring affect area and strength of femurs and mineral quantity but not strength of lumbar vertebrae in the offspring.

High folate gestational and post-weaning diets alter hypothalamic feeding pathways by DNA methylation in Wistar rat offspring.

Excess vitamins, especially folate, are consumed during pregnancy but later-life effects on the offspring are unknown. High multivitamin (10-fold AIN-93G, HV) gestational diets increase characteristics of metabolic syndrome in Wistar rat offspring. We hypothesized that folate, the vitamin active in DNA methylation, accounts for these effects through epigenetic modification of food intake regulatory genes. Male offspring of dams fed 10-fold folate (HFol) diet during pregnancy and weaned to recommended vitamin (RV) or HFol diets were compared with those born to RV dams and weaned to RV diet for 29 weeks. Food intake and body weight were highest in offspring of HFol dams fed the RV diet. In contrast, the HFol pup diet in offspring of HFol dams reduced food intake (7%, p = 0.02), body weight (9%, p = 0.03) and glucose response to a glucose load (21%, p = 0.02), and improved glucose response to an insulin load (20%, p = 0.009). HFol alone in either gestational or pup diet modified gene expression of feeding-related neuropeptides. Hypomethylation of the pro-opiomelanocortin (POMC) promoter occurred with the HFol pup diet. POMC-specific methylation was positively associated with glucose response to a glucose load (r = 0.7, p = 0.03). In conclusion, the obesogenic phenotype of offspring from dams fed the HFol gestational diet can be corrected by feeding them a HFol diet. Our work is novel in showing post-weaning epigenetic plasticity of the hypothalamus and that in utero programming by vitamin gestational diets can be modified by vitamin content of the pup diet.

High multivitamin intakes during pregnancy and postweaning obesogenic diets interact to affect the relationship between expression of PPAR genes and glucose regulation in the offspring.

High multivitamin intake (HV) during pregnancy increases body fat and weight and alters glucose and fatty acid metabolism in Wistar rat offspring. This study investigated the expression of peroxisome-proliferator activated receptors (PPARs) genes involved in regulation of glucose and fatty acid metabolism in their tissues. Dams received the AIN-93G diet with either the regular (RV) or 10-fold multivitamins (HV) during pregnancy. Male offspring were weaned to either the RV diet (RV-RV and HV-RV) or an obesogenic diet (RV-Ob and HV-Ob). Gene expression of PPARs in tissues was analyzed by real-time reverse transcriptase polymerase chain reaction. Gestational diet (GD) did not affect PPARs gene expression in offspring at either birth or weaning. In liver, at 14 weeks postweaning, PPAR-γ was 30% lower in the HV-RV and 30% higher in HV-Ob than in the RV-RV group [GD P=.76, postweaning diet (PD) P=.19, interaction P=.02, by two-way analysis of variance]. In muscle, PPAR-α expression was affected by GD and PD (GD P=.05, PD P<.01, interaction P=.07). In adipose tissue, PPAR-α expression was higher in all groups compared to RV-RV (GD P=.25, PD P=.85, interaction P=.03). PPAR-γ mRNA levels correlated with abdominal fat (r=0.45, P<.05) and insulin resistance index (r=0.39, P<.05). In liver, PPAR-γ expression correlated with insulin resistance index in offspring from RV (r=-0.62, P<.05), but not in those from HV dams (r=0.13, P>.05). In conclusion, the HV diet during pregnancy interacts with postweaning diets in determining the expression of PPARs genes in a tissue- and age-dependent manner and uncouples the relationship between these genes and glucose regulation and fat mass in the rat offspring.

Birth weight in children with birth defects.

BACKGROUND: Birth defects (BDs) are a serious public health problem in Mexico. The objective of this paper was to identify the frequency of newborns (NBs) that are born small for gestational age with a birth defect. MATERIALS AND METHODS: A cross-sectional study of NBs from hospitals part of the Mexican Institute of Social Security in Chihuahua, Mexico, was conducted. NBs were classified according to the presence or absence of a BD and according to their weight percentile using regional standards of birth weight. RESULTS: NBs diagnosed with (n = 263) or without BDs (n = 64,626) were included in this study. A greater proportion of NBs small for gestational age were identified in cases involving BDs (20%), compared with NBs without BDs (9%). Moreover, the average decrease in birth weights of NBs with BDs associated with their digestive system was 210 grams (95% confidence interval [CI], -436/-12), with their genital organs 440 grams (95% CI, -730/-151), involving chromosomal abnormalities 230 grams (95% CI, -435/-26), or with their musculoskeletal system 289 grams (95% CI, -43/-147) according to the gestational age, sex, and condition of the NB (p < 0.05). CONCLUSIONS: A greater proportion of NBs with BDs were associated with a low birth rate for their gestational age. In addition, some BDs were found to be associated with an impaired birth weight more often than others This suggests that clinical decisions regarding NBs with congenital defects and a lower birth weight for their gestational age should be diagnosed and treated for additional nutritional considerations as needed. Birth Defects Research (Part A), 2011. © 2011 Wiley-Liss, Inc.

A decreased n-6/n-3 ratio in the fat-1 mouse is associated with improved glucose tolerance.

A reduction in skeletal muscle fatty acid oxidation (FAO), manifested as a reduction in mitochondrial content and (or) FAO within mitochondria, may contribute to the development of insulin resistance. n-3 polyunsaturated fatty acids (PUFA) have been observed to increase the capacity for FAO and improve insulin sensitivity. We used the fat-1 mouse model, a transgenic animal capable of synthesizing n-3 PUFA from n-6 PUFA, to examine this relationship. Fat-1 mice exhibited a approximately 20-fold decrease in the n-6/n-3 ratio in skeletal muscle, and plasma glucose and the area under the glucose curve were significantly (p < 0.05) lower in fat-1 mice during a glucose challenge test. The improvement in whole-body glucose tolerance in the fat-1 mouse was associated with a approximately 21% (p < 0.05) decrease in whole-muscle citrate synthase (CS) activity (in red muscle only), without alterations in CS activity of isolated mitochondria (either red or white muscle; p > 0.05). These data suggest that the fat-1 mouse has decreased skeletal muscle mitochondrial content. However, the intrinsic ability of mitochondria to oxidize fatty acids was not altered in the fat-1 mouse, as rates of palmitate oxidation in isolated mitochondria from both red and white muscle were unchanged. Overall, this study demonstrates that a decrease in the n-6/n-3 ratio can enhance glucose tolerance in healthy animals, independent of changes in mitochondrial content.

Effects of exposure to pesticides during pregnancy on placental maturity and weight of newborns: a cross-sectional pilot study in women from the Chihuahua State, Mexico.

It is known that pesticides cross the placental barrier and can cause alterations in the development of placental structures resulting in adverse effects in reproduction. The objectives of this study were to investigate the effects of pesticide exposure during pregnancy on placental maturity and to evaluate the relationship between placental maturity, gestational age and birth weight. We collected the placentas from singleton pregnancies from women exposed (n = 9) and non-exposed (n = 45 full-term and n = 31 preterm) to pesticides as evaluated geographically, by questionnaire and by acetylcholinesterase levels. Placental morphometry from the central and peripheral regions was examined by microscopy and staining with hematoxylin and eosin. The placental maturity index (PMI) was estimated by dividing the number of epithelial plates in terminal villi to their thickness in 1 mm(2) of the placental parenchyma. Gestational age, birth weight and the following characteristics of the mother were also recorded: pre-pregnancy body mass index, weight gain during pregnancy and hemoglobin concentrations. Birth weight and the gestational age were correlated with PMI (r = .54 and r = .44, respectively; p < .01). Pesticide exposure was associated with a higher PMI (beta = 7.38, p = .01) after adjusting by variables related to placental maturity. In conclusion, the results suggest a relationship between prenatal exposure to pesticides and placental maturity and may potentially affect the nutrient transport from the mother to the fetus.