Perinatal programming of appetite regulation and metabolic health

According to the concept of perinatal programming environmental factors during fetal development and early postnatal life can influence phenotype in later life by modifying organ and tissue development and the epigenetic information of specific genes which, in turn, induce alteration in gene expression. Global nutrient restriction is a well-established intervention to study fetal programming but choline, a micronutrient essential for tissue growth and development, has not been extensively studied. The aim of this thesis is to investigate long term effects of modifications in maternal macro and micronutrient intake on the offsprings‟ appetite regulation and metabolic health. Twin-pregnant sheep were fed to requirements until 110 days of gestation and then randomised to stay on the same diet (R) or be restricted to 60% of caloric requirements (N) until term (~145 days). Offspring were subsequently subject either to a standard early postnatal growth rate as both twins remained with the mother (S) or to an accelerated growth rate resulting when only one twin remained to be mother fed (A). After weaning, offspring were reared in either a lean (L) or an obesogenic environment (O) until 17 months of age. These interventions gave rise to 4 groups: RAO, NAO, NSO and NSL. There were no differences in body weight, composition or adipocyte size with perinatal nutrient restriction but insulin response to a glucose tolerance test was increased in offspring born to N mothers. Measurement of hypothalamic gene expression in the latter offspring suggested a more orexigenic and cortisol-sensitive regulatory phenotype. During lactation, rats were fed a diet that was either choline-devoid (D), or contained a standard amount of choline either as bitartrate (C) or as phosphatidylcholine (PC). After weaning, female offspring were maintained on a standard choline diet until 11 weeks of age. D mothers had a substantial decrease in food intake and offspring were smaller at weaning but had similar glucose tolerance. Adult offsprings‟ brain phospholipid concentrations were reduced, which may suggest changes in brain development, but food intake and hypothalamic protein expression were unchanged. Intake of different forms of choline, i.e. bitartrate versus PC, during lactation had no long term effects on offspring. Both maternal dietary interventions had long term effects on offspring. Sheep developed the most adverse metabolic phenotype when the offspring were subjected to slow growth in late gestation followed by rapid growth and obesity, with the onset of insulin resistance mediated through changes in peripheral tissues. Maternal choline intake during lactation is essential for the health of the offspring as it alters brain composition. In conclusion, both studies produced results which are consistent with the concept of perinatal programming as adult metabolic health was affected in the sheep study and organ development was affected in a long term manner in the rat study

Perinatal programming of appetite regulation and metabolic health

According to the concept of perinatal programming environmental factors during fetal development and early postnatal life can influence phenotype in later life by modifying organ and tissue development and the epigenetic information of specific genes which, in turn, induce alteration in gene expression. Global nutrient restriction is a well-established intervention to study fetal programming but choline, a micronutrient essential for tissue growth and development, has not been extensively studied. The aim of this thesis is to investigate long term effects of modifications in maternal macro and micronutrient intake on the offsprings‟ appetite regulation and metabolic health. Twin-pregnant sheep were fed to requirements until 110 days of gestation and then randomised to stay on the same diet (R) or be restricted to 60% of caloric requirements (N) until term (~145 days). Offspring were subsequently subject either to a standard early postnatal growth rate as both twins remained with the mother (S) or to an accelerated growth rate resulting when only one twin remained to be mother fed (A). After weaning, offspring were reared in either a lean (L) or an obesogenic environment (O) until 17 months of age. These interventions gave rise to 4 groups: RAO, NAO, NSO and NSL. There were no differences in body weight, composition or adipocyte size with perinatal nutrient restriction but insulin response to a glucose tolerance test was increased in offspring born to N mothers. Measurement of hypothalamic gene expression in the latter offspring suggested a more orexigenic and cortisol-sensitive regulatory phenotype. During lactation, rats were fed a diet that was either choline-devoid (D), or contained a standard amount of choline either as bitartrate (C) or as phosphatidylcholine (PC). After weaning, female offspring were maintained on a standard choline diet until 11 weeks of age. D mothers had a substantial decrease in food intake and offspring were smaller at weaning but had similar glucose tolerance. Adult offsprings‟ brain phospholipid concentrations were reduced, which may suggest changes in brain development, but food intake and hypothalamic protein expression were unchanged. Intake of different forms of choline, i.e. bitartrate versus PC, during lactation had no long term effects on offspring. Both maternal dietary interventions had long term effects on offspring. Sheep developed the most adverse metabolic phenotype when the offspring were subjected to slow growth in late gestation followed by rapid growth and obesity, with the onset of insulin resistance mediated through changes in peripheral tissues. Maternal choline intake during lactation is essential for the health of the offspring as it alters brain composition. In conclusion, both studies produced results which are consistent with the concept of perinatal programming as adult metabolic health was affected in the sheep study and organ development was affected in a long term manner in the rat study

Beyond obesity - thermogenic adipocytes and cardiometabolic health

The global prevalence of obesity and related cardiometabolic disease continues to increase through the 21st century. Whilst multi-factorial, obesity is ultimately caused by chronic caloric excess. However, despite numerous interventions focussing on reducing caloric intake these either fail or only elicit short-term changes in body mass. There is now a focus on increasing energy expenditure instead which has stemmed from the recent ‘re-discovery’ of cold-activated brown adipose tissue (BAT) in adult humans and inducible ‘beige’ adipocytes. Through the unique mitochondrial uncoupling protein (UCP1), these thermogenic adipocytes are capable of combusting large amounts of chemical energy as heat and in animal models can prevent obesity and cardiometabolic disease. At present, human data does not point to a role for thermogenic adipocytes in regulating body weight or fat mass but points to a pivotal role in regulating metabolic health by improving insulin resistance as well as glucose and lipid homeostasis. This review will therefore focus on the metabolic benefits of BAT activation and the mechanisms and signalling pathways by which these could occur including improvements in insulin signalling in peripheral tissues, systemic lipid and cholesterol metabolism and cardiac and vascular function

The impact of image descriptions on user tagging behavior: A study of the nature and functionality of crowdsourced tags

Crowdsourcing has emerged as a way to harvest social wisdom from thousands of volunteers to perform a series of tasks online. However, little research has been devoted to exploring the impact of various factors such as the content of a resource or crowdsourcing interface design on user tagging behavior. Although images' titles and descriptions are frequently available in image digital libraries, it is not clear whether they should be displayed to crowdworkers engaged in tagging. This paper focuses on offering insight to the curators of digital image libraries who face this dilemma by examining (i) how descriptions influence the user in his/her tagging behavior and (ii) how this relates to the (a) nature of the tags, (b) the emergent folksonomy, and (c) the findability of the images in the tagging system. We compared two different methods for collecting image tags from Amazon's Mechanical Turk's crowdworkers - with and without image descriptions. Several properties of generated tags were examined from different perspectives: diversity, specificity, reusability, quality, similarity, descriptiveness, and so on. In addition, the study was carried out to examine the impact of image description on supporting users' information seeking with a tag cloud interface. The results showed that the properties of tags are affected by the crowdsourcing approach. Tags from the "with description" condition are more diverse and more specific than tags from the "without description" condition, while the latter has a higher tag reuse rate. A user study also revealed that different tag sets provided different support for search. Tags produced "with description" shortened the path to the target results, whereas tags produced without description increased user success in the search task

Hypergraph model of social tagging networks

The past few years have witnessed the great success of a new family of paradigms, so-called folksonomy, which allows users to freely associate tags to resources and efficiently manage them. In order to uncover the underlying structures and user behaviors in folksonomy, in this paper, we propose an evolutionary hypergrah model to explain the emerging statistical properties. The present model introduces a novel mechanism that one can not only assign tags to resources, but also retrieve resources via collaborative tags. We then compare the model with a real-world dataset: \emph{Del.icio.us}. Indeed, the present model shows considerable agreement with the empirical data in following aspects: power-law hyperdegree distributions, negtive correlation between clustering coefficients and hyperdegrees, and small average distances. Furthermore, the model indicates that most tagging behaviors are motivated by labeling tags to resources, and tags play a significant role in effectively retrieving interesting resources and making acquaintance with congenial friends. The proposed model may shed some light on the in-depth understanding of the structure and function of folksonomy.Comment: 7 pages,7 figures, 32 reference

Tissue cell stress response to obesity and its interaction with late gestational diet

Intra-uterine growth restriction in late pregnancy can contribute to adverse long term metabolic health in the offspring. We utilised an animal (sheep) model of maternal dietary manipulation in late pregnancy, combined with exposure of the offspring to a low activity, obesogenic environment after weaning, to characterise the effects on glucose homeostasis. Dizygotic twin-pregnant sheep were either fed to 60% of requirements (nutrient restriction (R)) or fed ad libitum (~ 140% of requirements (A)) from 110 days gestation until term (~147d). After weaning (~3 months of age), their offspring were kept in either a standard (in order to remain lean) or low activity, obesogenic environment. R mothers gained less weight and produced smaller offspring. As adults, obese offspring were heavier and fatter with reduced glucose tolerance, irrespective of maternal diet. Molecular markers of stress and autophagy in liver and adipose tissue were increased with obesity, with gene expression of hepatic Grp78 and of omental Atf6, Grp78 and Edem1 only being increased in R offspring. In conclusion, the adverse effect of juvenile onset obesity on insulin responsive tissues can be amplified by previous exposure to a suboptimal nutritional environment in utero, thereby contributing to earlier onset of insulin resistance

The haemodynamics of the human placenta in utero

© 2020 Dellschaft et al. We have used magnetic resonance imaging (MRI) to provide important new insights into the function of the human placenta in utero. We have measured slow net flow and high net oxygenation in the placenta in vivo, which are consistent with efficient delivery of oxygen from mother to fetus. Our experimental evidence substantiates previous hypotheses on the effects of spiral artery remodelling in utero and also indicates rapid venous drainage from the placenta, which is important because this outflow has been largely neglected in the past. Furthermore, beyond Braxton Hicks contractions, which involve the entire uterus, we have identified a new physiological phenomenon, the 'utero-placental pump', by which the placenta and underlying uterine wall contract independently of the rest of the uterus, expelling maternal blood from the intervillous space

Housing temperature modulates the impact of diet-induced rise in fat mass on adipose tissue before and during pregnancy in rats

Aim: To investigate whether housing temperature influences rat adiposity, and the extent it is modified by diet and/or pregnancy. Housing temperature impacts on brown adipose tissue, that possess a unique uncoupling protein (UCP) 1, which, when activated by reduced ambient temperature, enables rapid heat generation. Methods: We, therefore, examined whether the effects of dietary induced rise in fat mass on interscapular brown fat in female rats were dependent on housing temperature, and whether pregnancy further modulates the response. Four week old rats were either maintained at thermoneutrality (27°C) or at a “standard” cool temperature (20°C), and fed either a control or obesogenic (high in fat and sugar) diet until 10 weeks old. They were then either tissue sampled or mated with a male maintained under the same conditions. The remaining dams were tissue sampled at either 10 or 19 days gestation. Results: Diet had the greatest effect on fat mass at thermoneutrality although, by 19 days gestation, fat weight was similar between groups. Prior to mating, the abundance of UCP1 was higher at 20°C, but was similar between groups during pregnancy. UCP1 mRNA followed a similar pattern, with expression declining to a greater extent in the animals maintained at 20°C. Conclusion: Housing temperature has a marked influence on the effect of dietary induced rise in fat deposition that was modified through gestation. This maybe mediated by the reduction in UCP1 with housing at thermoneutrality prior to pregnancy and could subsequently impact on growth and development of the offspring

Dynamics of T2* and deformation in the placenta and myometrium during pre-labour contractions

Pre-labour uterine contractions, occurring throughout pregnancy, are an important phenomenon involving the placenta in addition to the myometrium. They alter the uterine environment and thus potentially the blood supply to the fetus and may thus provide crucial insights into the processes of labour. Assessment in-vivo is however restricted due to their unpredictability and the inaccessible nature of the utero-placental compartment. While clinical cardiotocography (CTG) only allows global, pressure-based assessment, functional magnetic resonance imaging (MRI) provides an opportunity to study contractile activity and its effects on the placenta and the fetus in-vivo. This study aims to provide both descriptive and quantitative structural and functional MR assessments of pre-labour contractions in the human uterus. A total of 226 MRI scans (18–41 weeks gestation) from ongoing research studies were analysed, focusing on free-breathing dynamic quantitative whole uterus dynamic T2* maps. These provide an indirect measure of tissue properties such as oxygenation. 22 contractile events were noted visually and both descriptive and quantitative analysis of the myometrial and placental changes including volumetric and T2* variations were undertaken. Processing and analysis was successfully performed, qualitative analysis shows distinct and highly dynamic contraction related characteristics including; alterations in the thickness of the low T2* in the placental bed and other myometrial areas, high intensity vessel-like structures in the myometrium, low-intensity vessel structures within the placental parenchyma and close to the chorionic plate. Quantitative evaluation shows a significant negative correlation between T2* in both contractile and not-contractile regions with gestational age (p 0.5). The quantitative and qualitative description of uterine pre-labour contractions including dynamic changes and key characteristics aims to contribute to the sparsely available in-vivo information and to provide an in-vivo tool to study this important phenomenon. Further work is required to analyse the origins of these subclinical contractions, their effects in high-risk pregnancies and their ability to determine the likelihood of a successful labour. Assessing T2* distribution as a marker for placental oxygenation could thus potentially complement clinically used cardiotocography measurements in the future