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1.
Objectives
To quantify the proportion of adverse pregnancy outcome attributable to maternal obesity.Design
Cross sectional analysis of routine obstetric dataset.Setting
Guy’s and St Thomas’s NHS Foundation Trust (GSTFT).Population
23,668 women who had singleton deliveries at GSTFT between 2004 and 2008.Methods
Logistic regression was used to estimate the association between BMI and outcome in different ethnic groups. Adjusted odds ratios, and the proportions of obese women, were used to calculate population attributable risk fractions (PAFs).Main Outcome Measures
(i) Maternal outcomes: diabetes, type of delivery, post-partum haemorrhage, and preterm delivery. (ii) Perinatal outcomes: macrosomia, low birth weight, admission to neonatal intensive care/special care baby unit, and perinatal death.Results
The prevalence of maternal obesity was 14%. Increasing BMI was independently associated with increasing risk of adverse obstetric and neonatal outcome. At the individual level, the effect of obesity on diabetes was highest in Asian women compared to white women (p for interaction = 0.03). Calculation of population attributable risk fractions demonstrated that one third of diabetes cases and one in six Caesarean sections could be avoided in this population if all obese women were of normal BMI. At the population level, the contribution of obesity to diabetes was highest for Black women (42%), and lowest for oriental women (8%). Seven percent of neonatal macrosomia in all the population, and 13% in Black mothers, were attributable to obesity.Conclusions
Preventing obesity prior to pregnancy will substantially reduce the burden of obstetric and neonatal morbidity in this population. This reduction will be higher in Black women. 相似文献2.
Deborah M. Sloboda Graham J. Howie Anthony Pleasants Peter D. Gluckman Mark H. Vickers 《PloS one》2009,4(8)
Background
While prepubertal nutritional influences appear to play a role in sexual maturation, there is a need to clarify the potential contributions of maternal and childhood influences in setting the tempo of reproductive maturation. In the present study we employed an established model of nutritional programming to evaluate the relative influences of prenatal and postnatal nutrition on growth and ovarian function in female offspring.Methods
Pregnant Wistar rats were fed either a calorie-restricted diet, a high fat diet, or a control diet during pregnancy and/or lactation. Offspring then were fed either a control or a high fat diet from the time of weaning to adulthood. Pubertal age was monitored and blood samples collected in adulthood for endocrine analyses.Results
We report that in the female rat, pubertal timing and subsequent ovarian function is influenced by the animal''s nutritional status in utero, with both maternal caloric restriction and maternal high fat nutrition resulting in early pubertal onset. Depending on the offspring''s nutritional history during the prenatal and lactational periods, subsequent nutrition and body weight gain did not further influence offspring reproductive tempo, which was dominated by the effect of prenatal nutrition. Whereas maternal calorie restriction leads to early pubertal onset, it also leads to a reduction in adult progesterone levels later in life. In contrast, we found that maternal high fat feeding which also induces early maturation in offspring was associated with elevated progesterone concentrations.Conclusions
These observations are suggestive of two distinct developmental pathways leading to the acceleration of pubertal timing but with different consequences for ovarian function. We suggest different adaptive explanations for these pathways and for their relationship to altered metabolic homeostasis. 相似文献3.
William R. Scott Cigdem Gelegen Keval Chandarana Efthimia Karra Ahmed Yousseif Chloé Amouyal Agharul I. Choudhury Fabrizio Andreelli Dominic J. Withers Rachel L. Batterham 《PloS one》2013,8(3)
Background
Neuronatin (NNAT) is an endoplasmic reticulum proteolipid implicated in intracellular signalling. Nnat is highly-expressed in the hypothalamus, where it is acutely regulated by nutrients and leptin. Nnat pre-mRNA is differentially spliced to create Nnat-α and -β isoforms. Genetic variation of NNAT is associated with severe obesity. Currently, little is known about the long-term regulation of Nnat.Methods
Expression of Nnat isoforms were examined in the hypothalamus of mice in response to acute fast/feed, chronic caloric restriction, diet-induced obesity and modified gastric bypass surgery. Nnat expression was assessed in the central nervous system and gastrointestinal tissues. RTqPCR was used to determine isoform-specific expression of Nnat mRNA.Results
Hypothalamic expression of both Nnat isoforms was comparably decreased by overnight and 24-h fasting. Nnat expression was unaltered in diet-induced obesity, or subsequent switch to a calorie restricted diet. Nnat isoforms showed differential expression in the hypothalamus but not brainstem after bypass surgery. Hypothalamic Nnat-β expression was significantly reduced after bypass compared with sham surgery (P = 0.003), and was positively correlated with post-operative weight-loss (R2 = 0.38, P = 0.01). In contrast, Nnat-α expression was not suppressed after bypass surgery (P = 0.19), and expression did not correlate with reduction in weight after surgery (R2 = 0.06, P = 0.34). Hypothalamic expression of Nnat-β correlated weakly with circulating leptin, but neither isoform correlated with fasting gut hormone levels post- surgery. Nnat expression was detected in brainstem, brown-adipose tissue, stomach and small intestine.Conclusions
Nnat expression in hypothalamus is regulated by short-term nutrient availability, but unaltered by diet-induced obesity or calorie restriction. While Nnat isoforms in the hypothalamus are co-ordinately regulated by acute nutrient supply, after modified gastric bypass surgery Nnat isoforms show differential expression. These results raise the possibility that in the radically altered nutrient and hormonal milieu created by bypass surgery, resultant differential splicing of Nnat pre-mRNA may contribute to weight-loss. 相似文献4.
Mohsen Besharat Pour Anna Bergstr?m Matteo Bottai Jessica Magnusson Inger Kull Magnus Wickman Tahereh Moradi 《PloS one》2014,9(10)
Background
Well documented diversity in risk of developing overweight and obesity between children of immigrant and of native mothers, might be explained by different body mass index (BMI) development trajectories in relation to maternal and perinatal characteristics of offspring.Objectives
To assess BMI development trajectories among children born to immigrant and to Swedish mothers from birth to adolescence in relation to perinatal characteristics.Methods
A cohort of 2517 children born in Stockholm during 1994 to 1996 was followed with repeated measurement of height and weight at eleven time points until age 12 years. We estimated changes over time for BMI in relation to maternal and perinatal characteristics of offspring using mixed linear model analysis for repeated measure data.Results
We observed a significant BMI change over time in children and time interaction with maternal migration status (P<0.0001). Estimated BMI over time adjusted for maternal and perinatal characteristics of offspring, showed slower BMI growth before age of 5, followed by an earlier plateau and steeper BMI growth after 5 years among children of immigrant mothers compared with children of Swedish mothers. These differences in BMI growth were more prominent among children with mothers from outside Europe.Conclusion
Beside reinforcing early childhood as a crucial period in development of overweight, the observed slower BMI development at early childhood among children of immigrants followed by a steeper increase in BMI compared with children of Swedish mothers is important for further studies and for planning of preventive public health programs. 相似文献5.
[Purpose]
This study suggests that the negative effects of inflammation caused by obesity could be prevented through diet restriction and exercise.[Methods]
In this study, 44 C57/BL6 male mice at about 4 weeks old (Orient bio, South Korea) were given a high fat diet for 5 weeks to make them obese. To help the mice lose weight, their dietary intake was limited and they were exercised on the treadmill for 8 weeks, and during that period, we analyzed the changes of MCP-1, ERK, Mn-SOD, HIF-1, and NOX in epididymal adipose tissue. There ND control group and obese group with high fat diet (HFD), and it is divided into four groups; HFD-ND-EX group, HFD-ND-nonEX group, HFD-DR-EX group and HFD-DR-nonEX group.[Results]
During their progress, the mRNA expressions of HIF-1α and ERK2 decreased, as did the expression of MCP-1 contained in the nucleus by suppressing oxygen free radicals, which was observed after the exercise program. However, dietary restriction without exercise training triggered an increase in the mRNA expression of MCP-1.[Conclusion]
To put this in perspective, combining exercise and dietary intake restriction likely prevented an influx of macrophages by reducing the number of fat cells, whereas only dietary restriction was not effective against reducing inflammation. 相似文献6.
7.
Background
Dietary supplementation with methyl donors can influence the programming of epigenetic patterns resulting in persistent alterations in disease susceptibility and behavior. However, the dietary effects of methyl donors on pain have not been explored. In this study, we evaluated the effects of dietary methyl donor content on pain responses in mice.Methods
Male and female C57BL/6J mice were treated with high or low methyl donor diets either in the perinatal period or after weaning. Mechanical and thermal nociceptive sensitivity were measured before and after incision.Results
Mice fed high or low methyl donor diets displayed equal weight gain over the course of the experiments. When exposed to these dietary manipulations in the perinatal period, only male offspring of dams fed a high methyl donor diet displayed increased mechanical allodynia. Hindpaw incision in these animals caused enhanced nociceptive sensitization, but dietary history did not affect the duration of sensitization. For mice exposed to high or low methyl donor diets after weaning, no significant differences were observed in mechanical or thermal nociceptive sensitivity either at baseline or in response to hindpaw incision.Conclusions
Perinatal dietary factors such as methyl donor content may impact pain experiences in later life. These effects, however, may be specific to sex and pain modality. 相似文献8.
Schulte DM Müller N Neumann K Oberhäuser F Faust M Güdelhöfer H Brandt B Krone W Laudes M 《PloS one》2012,7(2):e32437
Background
Obesity is associated with macrophage infiltration of adipose tissue. These inflammatory cells affect adipocytes not only by classical cytokines but also by the secreted glycopeptide wnt5a. Healthy adipocytes are able to release the wnt5a inhibitor sFRP5. This protective effect, however, was found to be diminished in obesity. The aim of the present study was to examine (1) whether obese human subjects exhibit increased serum concentrations of wnt5a and (2) whether wnt5a and/or sFRP5 serum concentrations in obese subjects can be influenced by caloric restriction.Methodology
23 obese human subjects (BMI 44.1±1.1 kg/m2) and 12 age- and sex-matched lean controls (BMI 22.3±0.4 kg/m2) were included in the study. Obese subjects were treated with a very low-calorie diet (approximately 800 kcal/d) for 12 weeks. Body composition was assessed by impedance analysis, insulin sensitivity was estimated by HOMA-IR and the leptin-to-adiponectin ratio and wnt5a and sFRP5 serum concentrations were measured by ELISA. sFRP5 expression in human adipose tissue biopsies was further determined on protein level by immunohistology.Principal Findings
Pro-inflammatory wnt5a was not measurable in any serum sample of lean control subjects. In patients with obesity, however, wnt5a became significantly detectable consistent with low grade inflammation in such subjects. Caloric restriction resulted in a weight loss from 131.9±4.0 to 112.3±3.2 kg in the obese patients group. This was accompanied by a significant decrease of HOMA-IR and leptin-to-adiponectin ratio, indicating improved insulin sensitivity. Interestingly, these metabolic improvements were associated with a significant increase in serum concentrations of the anti-inflammatory factor and wnt5a-inhibitor sFRP5.Conclusions/Significance
Obesity is associated with elevated serum levels of pro-inflammatory wnt5a in humans. Furthermore, caloric restriction beneficially affects serum concentrations of anti-inflammatory sFRP5 in such subjects. These findings suggest a novel regulatory system in low grade inflammation in obesity, which can be influenced by nutritional therapy. 相似文献9.
Background
A recent modeling study by the authors predicted that contextual information is poorly integrated into episodic representations in schizophrenia, and that this is a main cause of the retrieval deficits seen in schizophrenia.Methodology/Principal Findings
We have tested this prediction in patients with first-episode schizophrenia and matched controls. The benefit from contextual cues in retrieval was strongly reduced in patients. On the other hand, retrieval based on item cues was spared.Conclusions/Significance
These results suggest that reduced integration of context information into episodic representations is a core deficit in schizophrenia and one of the main causes of episodic memory impairment. 相似文献10.
Marc-Andre Cornier Andrea K. Salzberg Dawnielle C. Endly Daniel H. Bessesen Donald C. Rojas Jason R. Tregellas 《PloS one》2009,4(7)
Background
The regulation of energy intake is a complex process involving the integration of homeostatic signals and both internal and external sensory inputs. The objective of this study was to examine the effects of short-term overfeeding on the neuronal response to food-related visual stimuli in individuals prone and resistant to weight gain.Methodology/Principal Findings
22 thin and 19 reduced-obese (RO) individuals were studied. Functional magnetic resonance imaging (fMRI) was performed in the fasted state after two days of eucaloric energy intake and after two days of 30% overfeeding in a counterbalanced design. fMRI was performed while subjects viewed images of foods of high hedonic value and neutral non-food objects. In the eucaloric state, food as compared to non-food images elicited significantly greater activation of insula and inferior visual cortex in thin as compared to RO individuals. Two days of overfeeding led to significant attenuation of not only insula and visual cortex responses but also of hypothalamus response in thin as compared to RO individuals.Conclusions/Significance
These findings emphasize the important role of food-related visual cues in ingestive behavior and suggest that there are important phenotypic differences in the interactions between external visual sensory inputs, energy balance status, and brain regions involved in the regulation of energy intake. Furthermore, alterations in the neuronal response to food cues may relate to the propensity to gain weight. 相似文献11.
Background
Stresses like dietary restriction or various toxins increase lifespan in taxa as diverse as yeast, Caenorhabditis elegans, Drosophila and rats, by triggering physiological responses that also tend to delay reproduction. Food odors can reverse the effects of dietary restriction, showing that key mechanisms respond to information, not just resources. Such environmental cues can predict population trends, not just individual prospects for survival and reproduction. When population size is increasing, each offspring produced earlier makes a larger proportional contribution to the gene pool, but the reverse is true when population size is declining.Principal Findings
We show mathematically that natural selection can favor facultative delay in reproduction when environmental cues predict a decrease in total population size, even if lifetime fecundity decreases with delay. We also show that increased reproduction from waiting for better conditions does not increase fitness (proportional representation) when the whole population benefits similarly.Conclusions
We conclude that the beneficial effects of stress on longevity (hormesis) in diverse taxa are a side-effect of delaying reproduction in response to environmental cues that population size is likely to decrease. The reversal by food odors of the effects of dietary restriction can be explained as a response to information that population size is less likely to decrease, reducing the chance that delaying reproduction will increase fitness. 相似文献12.
Julienne N. Rutherford Victoria A. deMartelly Donna G. Layne Colon Corinna N. Ross Suzette D. Tardif 《PloS one》2014,9(5)
Background
The impact of the intrauterine environment on the developmental programming of adult female reproductive success is still poorly understood and potentially underestimated. Litter size variation in a nonhuman primate, the common marmoset monkey (Callithrix jacchus), allows us to model the effects of varying intrauterine environments (e.g. nutrient restriction, exposure to male womb-mates) on the risk of losing fetuses in adulthood. Our previous work has characterized the fetuses of triplet pregnancies as experiencing intrauterine nutritional restriction.Methodology/Principal Findings
We used over a decade of demographic data from the Southwest National Primate Research Center common marmoset colony. We evaluated differences between twin and triplet females in the number of pregnancies they produce and the proportion of those pregnancies that ended in fetal loss. We found that triplet females produced the same number of total offspring as twin females, but lost offspring during pregnancy at a significantly higher rate than did twins (38% vs. 13%, p = 0.02). Regardless of their own birth weight or the sex ratio of the litter the experienced as fetuses, triplet females lost more fetuses than did twins. Females with a male littermate experienced a significant increase in the proportion of stillbirths.Conclusions/Significance
These striking findings anchor pregnancy loss in the mother’s own fetal environment and development, underscoring a "Womb to Womb" view of the lifecourse and the intergenerational consequences of development. This has important translational implications for understanding the large proportion of human stillbirths that are unexplained. Our findings provide strong evidence that a full understanding of mammalian life history and reproductive biology requires a developmental foundation. 相似文献13.
Background
Numerosity estimation is a basic preverbal ability that humans share with many animal species and that is believed to be foundational of numeracy skills.It is notoriously difficult, however, to establish whether numerosity estimation is based on numerosity itself, or on one or more non-numerical cues like—in visual stimuli—spatial extent and density. Frequently, different non-numerical cues are held constant on different trials. This strategy, however, still allows numerosity estimation to be based on a combination of non-numerical cues rather than on any particular one by itself.Methodology/Principal Findings
Here we introduce a novel method, based on second-order (contrast-based) visual motion, to create stimuli that exclude all first-order (luminance-based) cues to numerosity. We show that numerosities can be estimated almost as well in second-order motion as in first-order motion.Conclusions/Significance
The results show that numerosity estimation need not be based on first-order spatial filtering, first-order density perception, or any other processing of luminance-based cues to numerosity. Our method can be used as an effective tool to control non-numerical variables in studies of numerosity estimation. 相似文献14.
Background
Intrauterine and postnatal overnutrition program hyperphagia, adiposity and glucose intolerance in offspring. Single-nucleotide polymorphisms (SNPs) of the fat mass and obesity associated (FTO) gene have been linked to increased risk of obesity. FTO is highly expressed in hypothalamic regions critical for energy balance and hyperphagic phenotypes were linked with FTO SNPs. As nutrition during fetal development can influence the expression of genes involved in metabolic function, we investigated the impact of maternal obesity on FTO.Methods
Female Sprague Dawley rats were exposed to chow or high fat diet (HFD) for 5 weeks before mating, throughout gestation and lactation. On postnatal day 1 (PND1), some litters were adjusted to 3 pups (vs. 12 control) to induce postnatal overnutrition. At PND20, rats were weaned onto chow or HFD for 15 weeks. FTO mRNA expression in the hypothalamus and liver, as well as hepatic markers of lipid metabolism were measured.Results
At weaning, hypothalamic FTO mRNA expression was increased significantly in offspring of obese mothers and FTO was correlated with both visceral and epididymal fat mass (P<0.05); body weight approached significance (P = 0.07). Hepatic FTO and Fatty Acid Synthase mRNA expression were decreased by maternal obesity. At 18 weeks, FTO mRNA expression did not differ between groups; however body weight was significantly correlated with hypothalamic FTO. Postnatal HFD feeding significantly reduced hepatic Carnitine Palmitoyltransferase-1a but did not affect the expression of other hepatic markers investigated. FTO was not affected by chronic HFD feeding.Significance
Maternal obesity significantly impacted FTO expression in both hypothalamus and liver at weaning. Early overexpression of hypothalamic FTO correlated with increased adiposity and later food intake of siblings exposed to HFD suggesting upregulation of FTO may contribute to subsequent hyperphagia, in line with some human data. No effect of maternal obesity was observed on FTO in adulthood. 相似文献15.
Objective
To determine the impact of sarcopenia and obesity on pulmonary function and quality of life (QOL) in chronic obstructive pulmonary disease (COPD) patients.Research Design and Methods
Data were obtained from the Korea National Health and Nutrition Examination Survey, including data from health interviews, health examinations, nutritional questionnaires, and laboratory findings. Laboratory data included pulmonary function assessment and dual energy X-ray absorptiometry results. Sarcopenia was measured by dual energy X-ray absorptiometry, and obesity was defined by body mass index. Male COPD patients were then classified into 4 groups according to the presence of sarcopenia and obesity.Results
In male patients with COPD, the prevalence of sarcopenia was found to be 29.3%, and that of sarcopenic obesity was 14.2%. Furthermore, 22.5% of the patients observed in this study had impaired QOL. Following multivariable statistical analysis, both sarcopenia and obesity were independent risk factors for worsening lung function. Adjusted values of forced vital capacity and forced expiratory volume in 1 second were the lowest in the sarcopenic obesity group. Sarcopenia was also associated with more subjective activity limitation and poorer QOL; however obesity was related to less subjective limitation and better QOL after multivariable analysis. Adjusted value of QOL was the lowest in sarcopenic subjects without obesity, and the highest in obese subject without sarcopenia.Conclusions
Both sarcopenia and obesity were found to be associated with worsening lung function in male COPD patients. However, obesity was positively correlated with improved QOL while sarcopenia was negatively correlated with QQL. 相似文献16.
17.
Cintra DE Ropelle ER Moraes JC Pauli JR Morari J Souza CT Grimaldi R Stahl M Carvalheira JB Saad MJ Velloso LA 《PloS one》2012,7(1):e30571
Background
In experimental models, hypothalamic inflammation is an early and determining factor in the installation and progression of obesity. Pharmacological and gene-based approaches have proven efficient in restraining inflammation and correcting the obese phenotypes. However, the role of nutrients in the modulation of hypothalamic inflammation is unknown.Methodology/Principal Findings
Here we show that, in a mouse model of diet-induced obesity, partial substitution of the fatty acid component of the diet by flax seed oil (rich in C18:3) or olive oil (rich in C18:1) corrects hypothalamic inflammation, hypothalamic and whole body insulin resistance, and body adiposity. In addition, upon icv injection in obese rats, both ω3 and ω9 pure fatty acids reduce spontaneous food intake and body mass gain. These effects are accompanied by the reversal of functional and molecular hypothalamic resistance to leptin/insulin and increased POMC and CART expressions. In addition, both, ω3 and ω9 fatty acids inhibit the AMPK/ACC pathway and increase CPT1 and SCD1 expression in the hypothalamus. Finally, acute hypothalamic injection of ω3 and ω9 fatty acids activate signal transduction through the recently identified GPR120 unsaturated fatty acid receptor.Conclusions/Significance
Unsaturated fatty acids can act either as nutrients or directly in the hypothalamus, reverting diet-induced inflammation and reducing body adiposity. These data show that, in addition to pharmacological and genetic approaches, nutrients can also be attractive candidates for controlling hypothalamic inflammation in obesity. 相似文献18.
Arianna Tocchetti Charlotte Blanche Ekalle Soppo Fabio Zani Fabrizio Bianchi Maria Cristina Gagliani Benedetta Pozzi Jan Rozman Ralf Elvert Nicole Ehrhardt Birgit Rathkolb Corinna Moerth Marion Horsch Helmut Fuchs Valérie Gailus-Durner Johannes Beckers Martin Klingenspor Eckhard Wolf Martin Hrabé de Angelis Eugenio Scanziani Carlo Tacchetti Giorgio Scita Pier Paolo Di Fiore Nina Offenh?user 《PloS one》2010,5(3)
Background
In a variety of organisms, including mammals, caloric restriction improves metabolic status and lowers the incidence of chronic-degenerative diseases, ultimately leading to increased lifespan.Methodology/Principal Findings
Here we show that knockout mice for Eps8, a regulator of actin dynamics, display reduced body weight, partial resistance to age- or diet-induced obesity, and overall improved metabolic status. Alteration in the liver gene expression profile, in behavior and metabolism point to a calorie restriction-like phenotype in Eps8 knockout mice. Additionally, and consistent with a calorie restricted metabolism, Eps8 knockout mice show increased lifespan. The metabolic alterations in Eps8 knockout mice correlated with a significant reduction in intestinal fat absorption presumably caused by a 25% reduction in intestinal microvilli length.Conclusions/Significance
Our findings implicate actin dynamics as a novel variable in the determination of longevity. Additionally, our observations suggest that subtle differences in energy balance can, over time, significantly affect bodyweight and metabolic status in mice. 相似文献19.
Fernanda Karina dos Santos José A. R. Maia Thayse Natacha Q. F. Gomes Timóteo Daca Aspacia Madeira Peter T. Katzmarzyk António Prista 《PloS one》2014,9(12)
Objectives
The purpose of this study was to examine secular changes in growth and nutritional status of Mozambican children and adolescents between 1992, 1999 and 2012.Methods
3374 subjects (1600 boys, 1774 girls), distributed across the three time points (523 subjects in 1992; 1565 in 1999; and 1286 in 2012), were studied. Height and weight were measured, BMI was computed, and WHO cut-points were used to define nutritional status. ANCOVA models were used to compare height, weight and BMI across study years; chi-square was used to determine differences in the nutritional status prevalence across the years.Results
Significant differences for boys were found for height and weight (p<0.05) across the three time points, where those from 2012 were the heaviest, but those in 1999 were the tallest, and for BMI the highest value was observed in 2012 (1992<2012, 1999<2012). Among girls, those from 1999 were the tallest (1992<1999, 1999>2012), and those from 2012 had the highest BMI (1999<2012). In general, similar patterns were observed when mean values were analyzed by age. A positive trend was observed for overweight and obesity prevalences, whereas a negative trend emerged for wasting, stunting-wasting (in boys), and normal-weight (in girls); no clear trend was evident for stunting.Conclusion
Significant positive changes in growth and nutritional status were observed among Mozambican youth from 1992 to 2012, which are associated with economic, social and cultural transitional processes, expressing a dual burden in this population, with reduction in malnourished youth in association with an increase in the prevalence of overweight and obesity. 相似文献20.
Schönbeck Y Talma H van Dommelen P Bakker B Buitendijk SE Hirasing RA van Buuren S 《PloS one》2011,6(11):e27608