Coming dissertations at Uppsala university
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Estrogen and its receptors in adipose tissue from women and men : Associations with age, adiposity and type 2 diabetes
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-524955
Obesity and its complications, such as insulin resistance and type 2 diabetes (T2D), are leading causes of morbidity and mortality globally. Adipose tissue is important for whole-body homeostasis, functioning as an energy storage reservoir and an endocrine organ. Estrogens mediate their effects through estrogen receptor alpha (ESR1) and beta (ESR2) and contribute to sex and menopause-related differences in body fat distribution. Moreover, estrogens can be produced from androgens in the adipose tissue by the enzyme aromatase. The overall aim of this thesis was to investigate the role of estrogen and estrogen signalling in human adipose tissue and their association with age, adiposity, and insulin resistance.
In Paper I, we assessed ESR1 and ESR2 gene expression in subcutaneous adipose tissue (SAT) from pre- and postmenopausal women, and investigated the effects of estradiol on adipocyte glucose uptake. We found that ESR2 gene expression was higher in postmenopausal women than premenopausal women. Moreover, in late, but not pre- or early postmenopausal women, estradiol incubation reduced basal and insulin-stimulated glucose uptake, which corresponded to an increase in ESR2 gene expression levels. The inhibiting effect of estradiol on adipocyte glucose uptake was prevented using an ESR2 antagonist.
Subsequently, in Paper II we assessed the role of ESR2 in SAT lipid and glucose metabolism and preadipocyte differentiation. ESR2 expression in SAT was inversely correlated with markers of central adiposity and positively correlated with markers of lipid accumulation. Moreover, ESR2 knockdown impaired subcutaneous preadipocyte differentiation and glucose utilization.
In Paper III, we focused on adipocyte lipolysis in women, which is regulated, in part, by catecholamines. OCT3, which mediates catecholamine transport into adipocytes, where they can be degraded, was increased in SAT with age, and higher in postmenopausal women than premenopausal women. Moreover, its expression was negatively associated with markers of insulin resistance and ex vivo lipolysis. Estradiol incubation of SAT downregulated OCT3 gene expression, which may explain lower OCT3 gene expression in premenopausal compared to postmenopausal women.
In Paper IV, we focused on the role of aromatase and estradiol in SAT from men. We found that aromatase expression was higher in SAT from men with obesity and T2D compared to subjects without obesity and T2D, respectively, and was positively associated with markers of central obesity and markers of insulin resistance. Contrastingly, ESR1 expression in SAT was lower in men with obesity and T2D compared to subjects without obesity and T2D, respectively, and negatively associated with markers of obesity and insulin resistance. ESR2 expression was higher in SAT from men with T2D compared to men without T2D. Estradiol reduced insulin-stimulated glucose uptake, however, neither testosterone, nor aromatase inhibition, altered adipocyte glucose uptake.
In this thesis, we found that estrogen has important metabolic effects in adipose tissue, including regulating lipid accumulation, glucose uptake capacity, and catecholamine transport. Overall, our findings suggest that estrogen and estrogen receptors may have an important role in age-, menopausal- and sex-dependent differences in body fat distribution, and may serve as potential targets for the prevention and treatment obesity and insulin resistance.
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The interaction of hydrogen with metallic glass
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-525370
Combining theoretical ab initio calculations with high-purity thin film sample synthesis and in situ measurements is a compelling way to bridge the gap in our understanding concerning hydrogen in metallic glasses, which is the primary work of this dissertation thesis. The main emphasis has been on how hydrogen affects the structure of metallic glasses, and how those changes influence not only the electronic properties of the amorphous metals but also their thermal stability.
The real-space correlations in the form of the pair distribution functions in thin metallic films have primarily only been accessible through synchrotron radiation. An effective methodological procedure using laboratory-based x-ray sources is here brought forth, which, for the first time, can produce accessible and accurate pair distribution functions from thin films down to a thickness of 80 nm.
The underpinning mechanisms behind the hydrogen-induced volume expansion of metallic glasses in the form of the dipole force tensor and an elastic hydrogen-hydrogen interaction were examined using in situ neutron reflectometry and first-principles calculations of expanding V80Zr20 amorphous structures. The dipole force tensor was concluded to be similar in magnitude to a mole-fraction-weighted sum of the ones found in hydrogen-contained vanadium and zirconium crystals, and the theoretical calculations demonstrated that it and the interaction energy varies with hydrogen concentration.
The electronic structure of the metallic glass V80Zr20 was determined via hard x-ray photoemission spectrometry and confirmed by first-principles calculations to be modified by the presence of hydrogen, in which a collection of s-d hybridized states 7 eV below the Fermi level was formed. The changes closer to the Fermi level, together with the volume expansion, were via experiments and ab initio calculations established to cause a parabolic change in resistance and a strong wavelength dependence on the optical transmission.
The thermal stability of amorphous VxZr1-x metals, investigated via ab initio calculations of the thermodynamic driving force towards crystallization, was found to affirm the observed hydrogen-induced enhancement in thermal stability.
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A View on the Invisible : A Study of Relationships between Different Aspects of Health in Populations
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-521129
This thesis studies relationships between different aspects of health. Health is a multi-faceted concept consisting of various aspects: most commonly morbidity, functional limitation, subjective health, and mortality. The relationships between these aspects, however, are not fully understood, so this thesis aims at contributing to our knowledge on the topic. Three studies are included, each with a particular aim within the general objective.
The first study is a systematic review of the articles that have attempted to study more than two aspects of health in one model. The review maps out the field of study, presenting and summarising the results of the articles selected to review, thereby also highlighting gaps in the research. One of its conclusions is that studies approaching health as one interconnected system are rare and that the relationships between the different aspects of health do not consistently show significant effects on each other. Additionally, many population groups in terms of age and place of residence are understudied. The findings from the systematic review have largely guided the scientific curiosity of the following two empirical studies.
The second study proposes and tests a parsimonious model of health structure consisting of morbidity, functional limitation, and subjective health on the adult respondents of European Social Survey (n=32,679) using structural equation modelling. The findings suggest that, in general, the proposed model holds true but there are age and gender differences in the health structure.
The third study explores the variations in the health structure of the adult population in 17 countries in three European regions (North, East, and West). The results show that the model does not apply in all the studied groups across the regions. Clear gender difference in health structure exist in the Western and Northern parts of Europe but not in the East. As to age groups, the analyses show that young adults are similar in their health structure across the regions while there are regional differences between the other two age groups.
This thesis shows that it is necessary to study the relationships between different aspects of health as one interconnected system. Furthermore, when health is at centre of scientific inquiry its multiple dimensions as well as age, gender, and regional variations should be acknowledged and taken into account.