The increasing prevalence of obesity and related health complications, such as type 2 diabetes, cardiovascular disease and cancer, demands thorough investigation of the underlying processes. One of the key tissues investigated in this context is adipose tissue. It is becoming increasingly clear that adipose tissue is a very dynamic and heterogenic organ. This thesis provides an overview of various aspects of adipose biology that illustrate its heterogenic nature and describes my own scientific contributions to this field. We typically distinguish between thermogenic, energy-expending brown adipocytes and energy-storing white adipocytes that are located in anatomically distinct adipose depots. In addition, brite (or beige) adipocytes are functionally thermogenic, but are located among white adipocytes. Related to functional variation, adipocytes and adipose tissues display a wide range of morphological appearances. An additional property that illustrates the heterogeneity among adipose cells and depots is the variation of cellular responses to physiological cues, such as changes in diet or environmental temperature. Furthermore, the developmental origins of various adipose types display great heterogeneity, which may explain some of the functional and dynamic differences that are observed. In line with the complexity of developmental origins, molecular markers that were initially proposed to distinguish between brown, brite/beige and white adipose subtypes have added to the notion that the composition of the adipose organ is much more complex than has long been appreciated. My own work has contributed to the enhancement of our understanding of the heterogeneity of adipose subtypes. In particular, my findings related to marker gene expression patterns have led to increased appreciation of the complex nature of adipose gene expression patterns and the complications of translating results obtained in mice to humans. Some of my other contributions have increased the understanding of the differences and similarities in thermogenic adipose tissue functionality and dynamics. With cell culture studies, I have revealed new characteristics of pre-adipose cells from various depots that further add to the appreciation of the adipose heterogeneity. Overall, this thesis provides an overview of important characteristics of the adipose organ, illustrating its heterogenic nature. Realization of this heterogeneity is of importance in order to properly study the adipose organ to ultimately understand how the adipose organ can be therapeutically targeted to effectively treat adipose-related diseases. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Manuscript. Paper 7: Manuscript. Paper 8: Manuscript.</p>

This research was undertaken primarily to further elucidate the life history of this medically important spider. Special attention was given to rearing experimental spiders under as near-natural environmental conditions as possible.

The thesis aims to provide an analysis of the legal limits imposed on brown coal exploitation in the Czech Republic, including an assessment of how these limits enter into particular stages of coal mining. The first chapter summarizes the applicable mining law legislation. The second chapter deals with restrictions set out by protection of the environment rules. Furthermore, the following chapter focuses on specific topic of so called ecological limits of exploitation. The fourth chapter points out the limits laid by the right of ownership. Finally, the thesis comprises a summary of contained conclusions.

We present an outline of basic assumptions and governing structural equations describing atmospheres of sub-stellar mass objects, in particular the extrasolar giant planets and brown dwarfs. Although most of the presentation of the physical and numerical background is generic, details of the implementation pertain mostly to the code COOLTLUSTY. We also present a review of numerical approaches and computer codes devised to solve the structural equations, and make a critical evaluation of their efficiency and accuracy.

In this work, we report the discovery of a candidate planetary-mass object with a photoevaporating protoplanetary disk, Proplyd. 133-353, which is near the massive star theta(1) Ori C at the center of the Orion Nebula Cluster (ONC). The object was known to have extended emission pointing away from theta(1) Ori. C, indicating ongoing external photoevaporation. Our near-infrared spectroscopic data and the location on the H-R diagram suggest that the central source of Proplyd. 133-353 is substellar (similar to M9.5) and has a mass probably less than 13 Jupiter mass and an age younger than 0.5 Myr. Proplyd. 133-353 shows a similar ratio of X-ray luminosity to stellar luminosity to other young stars in the ONC with a similar stellar luminosity and has a similar proper motion to the mean one of confirmed ONC members. We propose that Proplyd. 133-353 formed in a very low-mass dusty cloud or an evaporating gas globule near theta(1) Ori C as a second generation of star formation, which can explain both its young age and the presence of its disk.

Angular differential imaging provides a novel way of probing high contrast regions of our universe. Until now, its applications have been primarily localized to searching for exoplanets around nearby stars. This work presents a suite of applications of angular differential imaging from the theoretical underpinning of data reduction, to its use characterizing substellar objects, to a new application looking for the host galaxies of damped Lyman α systems which are usually lost in the glare of ultra-bright quasars along the line of sight. The search for exoplanets utilizes angular differential imaging and relies on complex algorithms to remove residual speckles and artifacts in the images. One such algorithm, the Template Locally Optimized Combination of Images (TLOCI), uses a least-squares method to maximize the signal-to-noise ratio and can be used with variable parameters, such as an input spectral template, matrix inversion method, aggressivity and unsharp mask size. Given the large volume of image sequences that need to be processed in any exoplanet survey, it is important to find a small set of parameters that can maximize detections for any conditions. Rigorous testing of these parameters were done with on-sky images and simulated inserted planets to find the optimal combination of parameters. Overall, a standard matrix inversion, along with two to three input templates, a modest aggressivity of 0.7 and the smallest unsharp mask was found to be the best choice to balance optimal detection. Beyond optimizations, TLOCI has been used in conjunction with angular differential imaging to characterize substellar objects in our local solar neighbourhood. In particular, the star HD 984 was imaged as a part of the Gemini Planet Imager Exoplanet Survey. Although previously known to have a substellar companion, new imaging presented here in the H and J bands help further characterize this object. Comparisons with a library of brown dwarf spectral types found a best match to HD 984 B of a type M7±2. Orbital fitting suggests an 18 AU (70 year) orbit, with a 68% confidence interval between 12 and 27 AU. Object magnitude was used to find the luminosity, mass and temperature using DUSTY models. Although angular differential imaging has proven its value in high contrast imaging, it has largely remained in the field of substellar object detection, despite other high contrast regimes in which it could be applied. One potential application is outside the local solar neighbourhood with studies of damped Lyman α systems, which have struggled to identify host galaxies thought to be caused by systems seen in the spectra of bright quasars. Work herein presents the first application of angular differential imaging to finding the host galaxies to damped Lyman α systems. Using ADI we identified three potential systems within 30kpc of the sightline of the quasar and demonstrate the potential for future imaging of galaxies at close separations. In summary, this thesis presents a comprehensive look at multiple aspects of high contrast angular differential imaging. It explores optimizations with a data reduction algorithm, implementations characterizing substellar objects, and new applications imaging galaxies. / Graduate

Faculty of Science School of Geography And Archaeology and Enviromental Studies 9905693x Nicola@crg.bpb.wits.ac.za / The Cape Town brown haze is a brown-coloured smog that is present over the Cape Town atmosphere during the winter months due to the accumulation of gaseous and particulate pollutants. The main aim of this research was to evaluate the impact of atmospheric pollutants to visibility impairment by the brown haze through visibility modelling of major pollution sources around the City of Cape Town. The screening model, VISCREEN, the Plume Visibility model, PLUVUE II and the CALPUFF Modelling System were employed to model the visual impact of emissions from the major sources. Two point sources, Caltex Oil Refinery and Consol Glass, and three area sources, Cape Town Central Business District (CBD), Cape Town International Airport and the townships of Khayelitsha and Mitchell’s Plain were identified as the major sources. An initial screening analysis indicated that emissions from the two industrial sources would be visible and would result in a yellow-brown discolouration of the atmosphere. Detailed modelling using PLUVUE II identified the area sources of Cape Town CBD and the townships to be the significant contributors to visibility impairment over Cape Town. Plume perceptibility is primarily dependant upon particulate emissions while NOx emissions influence the colouration of the atmosphere. CALPUFF was employed to assess the distribution of NOx, SO2 and PM10 concentrations over the area and the associated visibility impairment on a nonhaze (13 August 2003) and haze day (22 August 2003). Pollutant concentrations were considerably reduced on the non-haze day compared to the haze day. The Cape Town CBD was an important source of all the major pollutants with the townships contributing significantly to the aerosol loading over Cape Town. Pollutant concentrations are particularly elevated during the late evening and early morning periods, particularly between 7 am and 8 am. Visibility impairment is greatest on the haze day, particularly over the central Cape Town region and the townships. The greatest reduction in visibility is experienced between midnight and 9 am which corresponds with the periods of elevated atmospheric pollutant concentrations.

Os escorpiões são únicos dentre os artrópodes terrestres em muitos aspectos da biologia reprodutiva. A corte em escorpiões envolve sequências complexas de comportamentos ritualizados; é dividida em três fases: iniciação, dança e transferência de espermatozoides. Cerca de 50 espécies de escorpiões dentre as 1600 atualmente reconhecidas tiveram a corte descrita. Do mesmo modo, são poucos os estudos com tamanho de prole e investimento reprodutivo em escorpiões. Até o momento, a descrição da corte em Tityus bahiensis foi realizada com base em poucas observações incompletas. Os objetivos deste trabalho foram: estudar a corte em T. bahiensis para reconhecer os repertórios comportamentais e padrões de comportamento para espécie, através de um etograma e de um fluxograma; investigar prováveis funções das categorias comportamentais; abordar aspectos da época reprodutiva; e estudar o tamanho de prole, tempo de gestação e investimento reprodutivo. Dezenove cortes, de 202 pareamentos realizados, foram utilizadas para elaboração do etograma e do fluxograma. As sequências de comportamentos foram analisadas com o programa JWacher sup TM/sup e compiladas através de um script em Perl. Para o estudo do tamanho de prole, data de nascimento e período de gestação, foram compilados dados de 76 fêmeas. Desses nascimentos, 12 foram provenientes de cortes observadas em laboratório. A corte em T. bahiensis é complexa e está organizada de modo que a realização de uma fase prepara e condiciona o aparecimento da seguinte. A fase de iniciação tem funções como a procura por parceiros sexuais e o reconhecimento específico, sexual e da predisposição dos parceiros à corte. A fase de dança é dividida em dois módulos. No módulo I, o macho estimula e conduz a fêmea a uma superfície adequada para deposição do espermatóforo, preferencialmente uma casca de árvore (X2=24,314; g.l.=5; p<0,001). O módulo II apresenta comportamentos frequentes e repetitivos, com a função de estimular a fêmea e preparála para a fase seguinte. A fase de transferência de espermatozoides é rápida e estereotipada. Tem a função de inseminar e estimular a fêmea para uma cópula bemsucedida. Durante a cópula, o macho executa cortejo copulatório (tateamento com pernas e roçar com quelíceras). A fase de pós-transferência segue um padrão, mas apresenta poucas categorias, sendo que a maioria tem a provável função de romper o flagelo do espermatóforo inserido no gonóporo do macho; o macho pode consumir o espermatóforo e não ocorre canibalismo sexual. As fêmeas de T. bahiensis são capazes de controlar diferentes fases da corte obrigando os machos a utilizar comportamentos de estímulo, ao invés de coerção, para serem aceitos. A exibição de cortejo copulatório pelos machos é um forte indicativo da existência de seleção críptica feminina em T. bahiensis, sendo uma estratégia reprodutiva para estimular a fêmea a aceitar os espermatozoides do macho durante a aquisição do esperma. Apesar da época reprodutiva compreender o ano todo, os meses de maior atividade sexual são novembro a abril. O tamanho de prole na primeira parição é 2-25 filhotes (n=76). Além disso, T. bahiensis é capaz de produzir 1-4 proles com uma inseminação. O tempo de gestação é 2,5-12,8 meses e, apesar da capacidade de parir o ano todo, a maioria das parições ocorreu nos meses quentes, sobretudo, entre novembro e janeiro (X2=164,912; g.l.=11; p<0,001). Adicionalmente, o tamanho de prole é correlacionado com o tamanho corpóreo materno (rs=0,593; p=0,042; n=12). Assim, fêmeas maiores produzem mais filhotes e, portanto, apresentam maior investimento reprodutivo. / Scorpions are unique among terrestrial arthropods in many reproductive biology traits. Courtship involves a complex series of ritualized behaviors; it is divided into three phases: initiation, Promenade à deux, and sperm transfer. Courtship behavior has been described for about 50 of the 1600 extant scorpion species. Likewise, litter size and reproductive investment in scorpions are poorly known. Previous studies on Tityus bahiensis described courtship based on few and incomplete observations. The aims of this work were to study courtship behavior in T. bahiensis in order to recognize behavior repertories and behavior patterns for the species by making an ethogram and fluxogram; investigate probable functions of behavior categories; address aspects of the reproductive season; and study litter size, gestation period, and reproductive investment. Nineteen courtships, out of 202 interactions, were used to make the ethogram and the fluxogram. Behavioral sequences were analyzed with JWacherTM and compiled by a Perl script. For the study of litter size, date of birth, and gestation period, data of 76 females were compiled. Of these, 12 births were obtained from courtship observed in the laboratory. Courtship in T. bahiensis is complex and it is organized in a way that the execution of one phase prepares and regulates the appearance of the next. Initiation phase has functions such as the search for mating partner and species, sexual, and predisposition to court recognition. Promenade à deux phase is divided into two modules. In module I, male stimulates and leads female to a suitable surface for spermatophore deposition, preferentially a bark (X2=24,314; g.l.=5; p<0,001). Module II is characterized by frequent and repetitive behaviors, with the function of stimulating the female and preparing her to the next phase. Sperm transfer phase is rapid and stereotyped. Its function is to inseminate and stimulate the female for a successful mate. During mate, male executes copulatory courtship (feeling and kissing). Post transfer phase has a pattern, but with feel categories; most of them has the probable function of breaking the spermatophore flagellum inserted in the male gonopore; male may consume spermatophore, and there is no mating cannibalism. The females of T. bahiensis are capable of controlling different courtship phases, engaging males to use stimulating behaviors, rather than coercion, to be accepted. The exhibition of copulatory courtship by males strongly indicates the existence of cryptic female choice in T. bahiensis, being a reproductive strategy to stimulate the female to accept male spermatozoids during sperm uptake. Although reproductive season takes place all year long, the months in which reproductive activity is greater are throughout November to April. Litter size at the first parturition is 2-25 offspring (n=76). Moreover, T. bahiensis is capable of producing 1-4 broods with a single insemination. Gestation period is 2,5-12,8 months, and, although the capacity of giving birth throughout the year, most of the parturition occurred in the warm season, specially throughout November to January (X2=164,912; g.l.=11; p<0,001). In addition, litter size is correlated to female body size (rs=0,593; p=0,042; n=12). Thus, larger females produce more offspring and invest more into reproduction.

Ellen Lai Ping Chan. / Thesis (Ph.D)--Chinese University of Hong Kong, 1990. / Bibliography: leaves 238-272. / Chapter CHAPTER I --- LITERATURE REVIEW / Chapter 1. --- History --- p.1 / Chapter 2. --- Species Distribution of BAT --- p.3 / Chapter 3. --- Distribution of BAT --- p.4 / Chapter 4. --- Structure of BAT --- p.4 / Chapter 4.1. --- Macroscopic Appearance --- p.4 / Chapter 4.1.1. --- Innervation --- p.4 / Chapter 4.1.2. --- Blood supply --- p.5 / Chapter 4.2. --- Microscopic Structure of BAT --- p.6 / Chapter 4.3. --- Difference Between Brown Fat and White Fat --- p.9 / Chapter 5. --- Composition of BAT --- p.11 / Chapter 6. --- The Mechanisms of Brown Adipose Tissue Thermogenesis --- p.12 / Chapter 6.1. --- Factors Influencing Proton Transport by UCP --- p.16 / Chapter 6.2. --- Postulated Sequence of Events during Thermogenesis --- p.18 / Chapter 7. --- Measurements of thermogenic Capacity of BAT --- p.21 / Chapter 8. --- Age-related Differences in BAT --- p.28 / Chapter 9. --- Non-shivering Thermogenesis and BAT --- p.32 / Chapter 9.1. --- Changes In BAT During Cold Acclimation --- p.35 / Chapter 9.1.1. --- GDP Binding --- p.35 / Chapter 9.1.2. --- Concentration of UCP --- p.37 / Chapter 9.1.3. --- Metabolic changes in BAT during Cold Acclimation --- p.39 / Chapter 10. --- Diet-induced Thermogenesis and BAT --- p.41 / Chapter 10.1. --- Mechanism of DIT --- p.42 / Chapter 10.2. --- Controversies in DIT --- p.44 / Chapter 10.3. --- Nutritional Factors Inducing DIT --- p.46 / Chapter 10.4. --- DIT in Man --- p.47 / Chapter 10.5. --- Neuroendocrine Control of BAT in DIT --- p.48 / Chapter 10.6. --- Effects of Fasting in BAT --- p.51 / Chapter 11. --- Obesity and BAT --- p.53 / Chapter 11.1. --- NST and DIT in Obese Animals --- p.58 / Chapter 11.2. --- Regulation of BAT in Obese Animals --- p.59 / Chapter 11.2.1. --- Sympathetic Nervous System in Obese Animals --- p.59 / Chapter 11.2.2. --- Corticosteriods in Obese Animals --- p.61 / Chapter 11.2.3. --- Adrenergic Receptors in Obese Animals --- p.63 / Chapter 11.2.4. --- Insulin in Obese Animals --- p.64 / Chapter 12. --- Pregnancy and Lactation and BAT --- p.67 / Chapter 12.1. --- Energy Balance During Pregnancy and Lactation --- p.67 / Chapter 12.2. --- Some Metabolic Changes During X Pregnancy and Lactation --- p.68 / Chapter 12.3. --- Role of BAT in Pregnancy and Lactation --- p.70 / Chapter 12.4. --- Mechanism of Regulation of Thermogenesis during Pregnancy and Lactation --- p.71 / Chapter 13. --- Factors Controlling the Thermogenesis --- p.75 / Chapter 13.1. --- Sympathetic Nervous Control --- p.75 / Chapter 13.1.1. --- Studies of Administration of Noradrenaline --- p.75 / Chapter 13.1.2. --- Control of the Fuel Supply to BAT by Sympathetic Nervous System --- p.77 / Chapter 13.1.3. --- Sympathetic denervation --- p.78 / Chapter 13.2. --- Hormonal Control --- p.79 / Chapter 13.2.1. --- Thyroid Hormone --- p.79 / Chapter 13.2.2. --- Insulin --- p.81 / Chapter 13.2.3. --- Pituitary Hormones --- p.83 / Chapter 13.2.4. --- Glucocorticoids --- p.83 / Chapter 13.2.5. --- Corticotropin-Releasing Factor --- p.85 / Chapter 14. --- Aims of the Study --- p.87 / Chapter CHAPTER II --- ISOLATION AND PURIFICATION OF UCP AND DEVELOPMENT OF AN ENZYME LINKED IMMUNOSORBENT ASSAY FOR UCP / Chapter 1. --- INTRODUCTION --- p.88 / Chapter 2. --- MATERIALS AND METHODS --- p.89 / Chapter 2.1. --- Animals --- p.89 / Chapter 2.2. --- Collection of BAT --- p.89 / Chapter 2.3. --- Isolation of Mitochondria --- p.90 / Chapter 2.4. --- Electron Microscopy (EM) of Isolated BAT Mitochondria --- p.92 / Chapter 2.5. --- Measurement of Protein and Cytochrome C Oxidase Activity --- p.94 / Chapter 2.5.1. --- Measurement of Protein Concentration --- p.94 / Chapter 2.5.2. --- Measurement of Cytochrome C Oxidase Activity --- p.99 / Chapter 2.6. --- GDP Binding Assay of BAT Mitochondria --- p.101 / Chapter 2.6.1. --- GDP Binding Assay of Mitochondria by Centrifugation Method --- p.103 / Chapter 2.6.2. --- GDP: Binding Activity by Equilibrium Dialysis --- p.106 / Chapter 2.6.3. --- GDP Binding by Microfiltration Method --- p.108 / Chapter 2.7. --- Experiments Designed for Validation of GDP Binding Assay --- p.109 / Chapter 2.7.1. --- GDP Binding Activity in BAT Mitochondria after Noradrenaline Treatment --- p.109 / Chapter 2.7.2. --- GDP Binding Activity in BAT Mitochondria after Cold Acclimation and Noradrenaline Treatment --- p.110 / Chapter 2.7.3. --- Effect of Food Restriction on Cold Acclimated Rats --- p.110 / Chapter 2.7.4. --- GDP Binding Activity of BAT Mitochondria of Rats of Different Ages --- p.111 / Chapter 2.8. --- Isolation and Purification of UCP --- p.111 / Chapter 2.9. --- Sodium Dodecyl Sulphate-Polyacrylamide Gel Electrophoresis (SDS-PAGE) --- p.115 / Chapter 2.10. --- Methods for Raising Anti-Rat-UCP Antibody and the Characterization of Antiserum --- p.120 / Chapter 2.10.1. --- Raising Rabbit Anti-Rat-UCP Antibody --- p.120 / Chapter 2.10.2. --- Western Blot Analysis For Cross Reactivity Study --- p.120 / Chapter 2.10.3. --- Immuno-Autoradiographic Method for Detection of Specificity of Rabbit Anti-Rat UCP Antiserum --- p.121 / Chapter 2.11. --- Enzyme Linked Immunosorbent Assay For UCP --- p.124 / Chapter 2.12. --- Experiment Designed to Validate the ELISA --- p.129 / Chapter 2.13. --- Statistical Analysis --- p.129 / Chapter 3. --- RESULTS --- p.130 / Chapter 3.1. --- Electron Microscopy of Isolated BAT Mitochondria --- p.130 / Chapter 3.2. --- GDP Binding Assay of BAT Mitochondria --- p.130 / Chapter 3.3. --- Experiments Designed for Validation of GDP Binding Assay --- p.133 / Chapter 3.3.1. --- GDP Binding Activity of BAT Mitochondria after Noradrenaline Injection --- p.133 / Chapter 3.3.2. --- GDP Binding Activity of BAT Mitochondria after Cold Acclimation and Noradrenaline Treatment --- p.136 / Chapter 3.3.3. --- Effects of Food Restriction on Cold Acclimated Rats --- p.136 / Chapter 3.3.4. --- GDP Binding Activity of BAT Mitochondria from Rats of Different Ages --- p.140 / Chapter 3.4. --- Isolation and Purification of UCP --- p.140 / Chapter 3.4.1. --- Results of SDS-PAGE --- p.143 / Chapter 3.4.2. --- Results of GDP Binding Activity --- p.149 / Chapter 3.5. --- Rabbit Anti-rat-UCP Antibody and the Characterization of Antiserum --- p.151 / Chapter 3.5.1. --- Immuno-autoradiography for Specificity of Rabbit Anti-rat-UCP Antiserum --- p.153 / Chapter 3.5.1.1. --- Cross-reactivity of the Rabbit Anti-rat-UCP Antiserum to Mitochondrial Proteins of BAT and from other Tissues --- p.153 / Chapter 3.5.1.2. --- Cross-reactivity of the Rabbit Anti-rat-UCP Antiserum to BAT Mitochondrial Protein from Different Rodent Species --- p.156 / Chapter 3.5.1.3. --- Dose Response of Rabbit Anti-rat-UCP Antiserum to UCP --- p.159 / Chapter 3.6. --- ELISA of UCP --- p.161 / Chapter 3.6.1. --- Determination of Maximum Amount of UCP Binding on Microtitre Plate --- p.161 / Chapter 3.6.2. --- Antibody Dilution Curve --- p.161 / Chapter 3.6.3. --- Incubation Time for Enzyme-Substrate Reaction --- p.163 / Chapter 3.6.4. --- Competitive ELISA --- p.163 / Chapter 3.6.5. --- Precision of ELISA --- p.167 / Chapter 3.7. --- Experiment Designed for Validation of ELISA by Measuring UCP in Cold Acclimated Rats --- p.170 / Chapter 4. --- DISCUSSION --- p.172 / Chapter 4.1. --- GDP Binding Assay of BAT Mitochondria --- p.172 / Chapter 4.2. --- Isolation and Purification of UCP --- p.176 / Chapter 4.3. --- Development and Evaluation of ELISA --- p.178 / Chapter CHAPTER III --- CHANGES IN BAT DURING PREGNANCY AND LACTATION AND ROLE OF PROLACTIN / Chapter 1. --- INTRODUCTION --- p.184 / Chapter 2. --- MATERIALS AND METHODS --- p.187 / Chapter 2.1. --- Animal --- p.187 / Chapter 2.2. --- Experimental Designs --- p.187 / Chapter 2.2.1. --- "Effects of Pregnancy, Lactation and Post Weaning on BAT" --- p.187 / Chapter 2.2.2. --- Effect of Metoclopramide on BAT --- p.188 / Chapter 2.2.3. --- Effect of Metoclopramide and Bromocriptine on BAT --- p.188 / Chapter 2.2.4. --- Effect of PRL Injection on BAT --- p.189 / Chapter 2.2.5. --- Continuous infusion of PRL --- p.189 / Chapter 2.6.6. --- Measurements of BAT Parameters --- p.191 / Chapter 2.2.7. --- RIA of serrum PRL --- p.191 / Chapter 2.2.8. --- PRL Receptors in BAT --- p.197 / Chapter 2.4. --- Statistical Analysis --- p.201 / Chapter 3. --- RESULTS --- p.202 / Chapter 3.1. --- Effects of Pregnancy and Lactation --- p.202 / Chapter 3.1.1. --- Food Consumption and Body Weight --- p.202 / Chapter 3.1.2. --- BAT --- p.205 / Chapter 3.1.3. --- Serum PRL level --- p.209 / Chapter 3.2. --- Effects of PRL njection --- p.213 / Chapter 3.3. --- Effects of Continuous Infusion of PRL on BAT --- p.213 / Chapter 3.4. --- Effects of Metoclopramide on BAT --- p.216 / Chapter 3.5. --- Effects of Bromocriptine and Metoclopramide on BAT --- p.216 / Chapter 3.6. --- PRL Receptor in BAT --- p.219 / Chapter 4. --- DISCUSSION --- p.223 / GENERAL CONCLUSION --- p.236

Brown and beige fat are specialized adipose tissues found in almost all mammals that can increase energy expenditure and produce heat. Cold exposure and b3-adrenergic stimulation has been extensively shown to activate brown adipose tissue (BAT) in rodents, which promotes uncoupled respiration of glucose and lipid substrates via uncoupling protein 1 (UCP1). Prolonged stimulation can induce white adipose browning, which leads to the emergence of thermogenic cells within white fat depots, called beige adipocytes. The beige adipocyte possesses a unique molecular signature, yet shares several characteristics of brown adipocytes, including high mitochondrial content. When activated, beige fat can be induced to initiate a thermogenic transcriptional program similar to that of BAT. Recent human studies have identified brown and/or beige fat in the supraclavicular region using various radiation imaging modalities. This remarkable discovery has reinvigorated scientific interest in adipose browning and brown/beige fat activation as possible therapeutic targets for obesity. Like in rodents, several groups have previously tested the potential impact of cold exposure and b3-adrenergic agonism on BAT-mediated thermogenesis in humans. However, even though these approaches were shown to significantly increase energy expenditure and promote weight loss in obese individuals, they are not ideal clinical interventions. Cold exposure is uncomfortable and requires prolonged treatment, while b3-adrenergic agonists may lead to many adverse effects like cardiovascular problems. This thesis will evaluate the therapeutic potential and clinical relevance of alternative anti-obesity approaches that target adipose browning and beige adipose activation.