A contribuição genética para o desenvolvimento da obesidade precisa ser esclarecida em intervenções para perda de peso, como é o caso da cirurgia bariátrica. Portanto, a análise da expressão gênica relacionada ao gasto energético e posterior associação com a taxa metabólica de repouso pode elucidar o entendimento de fatores genéticos que contribuem para a obesidade. Além disso, as informações genéticas expressas em determinados indivíduos, podem ajudar a esclarecer mecanismos relacionados à regulação energética e oxidação de substratos. Assim, o objetivo do presente trabalho foi verificar a expressão dos genes ADRB3, UCPs, PLIN1, PPARG2, em tecido adiposo subcutâneo abdominal e associar com medidas da taxa metabólica de repouso em indivíduos obesos grau III antes e após cirurgia bariátrica. A amostra foi composta por 13 mulheres com obesidade antes e após 6 meses de cirurgia bariátrica pela técnica de derivação gástrica em Y de Roux e 10 mulheres eutróficas. Tratou-se de um estudo longitudinal, no qual foram coletadas medidas antropométricas de peso, estatura, índice de massa corporaI, circunferência abdominal, composição corporal (massa corporal magra e massa gorda) pela bioimpedância elétrica, calorimetria indireta para mensurar a taxa metabólica de repouso e análise de expressão gênica pela técnica de PCR em tempo real. Foram observadas diferenças nas variáveis de peso, índice de massa corporal, circunferência abdominal, massa corporal magra, massa gorda e taxa metabólica de repouso entre os grupos do estudo. Houve diminuição dos valores absolutos da taxa metabólica de repouso (2.094±275 vs 1.863±210kcal, p=0,01), porém quando ajustada pelo peso observou-se aumento (17,7±2,1 vs 20,4±2,1kcal/kg p=0,01). A massa corporal magra no momento pós operatório exerceu influência de 29% na taxa metabólica de repouso por quilograma de peso, sendo que houve correlação positiva entre as duas variáveis (r=0,63, p=0,02). A expressão do gene UCP2 apresentou diferença entre os dois momentos do estudo (p=0,01). Houve influência dos genes UCP2 e PLIN1 na taxa metabólica de repouso por quilograma de peso no período pré operatório. O percentual de perda de peso foi influenciado pela expressão dos genes UCP2 e PLIN1 no período pré operatório. Conclui-se que as modificações proporcionadas pela cirurgia bariátrica aumentam a expressão dos genes e gasto energético de mulheres com obesidade grau III. / The contribution of genetic to the development of obesity need to be established accurately interventions for weight loss, as in the case of bariatric surgery. Therefore, the analysis of gene expression related to energy expenditure and subsequent association with the resting metabolic rate can elucidate the understanding of genetic factors that contribute to obesity. Furthermore, the genetic information expressed in certain individuals may help clarify regulatory mechanisms related to energy and substrate oxidation. The objective was to investigate the expression of genes ADRB3, UCPs, PLIN1 and PPARG2 in abdominal subcutaneous adipose tissue and associate it with measures of resting metabolic rate in grade III obese patients before and after bariatric surgery. The sample consisted of 13 obese women before and 6 months after bariatric surgery (gastric bypass Roux-Y technique) and 10 healthy women. This was a longitudinal study in which anthropometric measurements of weight were collected, height, body mass index, waist circumference, body composition (lean body mass and fat mass) by bioelectrical impedance, indirect calorimetry to measure the resting metabolic rate and gene expression was analysed by PCR real time. Differences in body weight, body mass index, waist circumference, lean body mass, fat mass and resting metabolic rate between the study groups. There was a decrease of the absolute values of the resting metabolic rate (2.094±275 vs 1863±210kcal, p=0,01), but when adjusted for body weight an increase was observed (17,7±2,1 vs 20,4±2,1kcal/kg p=0,01). Lean body mass in the post operative period influenced 29% in resting metabolic rate per kilogram of weight, and there was a positive correlation between resting metabolic rate and lean body mass (r=0,63, p=0,02). The expression of UCP2 gene was different between the two sample points (p=0,01). There was influence of UCP2 and PLIN1 genes in resting metabolic rate per kilogram of weight in the preoperative period. The percentage of weight loss was influenced by the UCP2 gene and PLIN1 preoperative period. We conclude that the modifications provided by bariatric surgery increase the gene expression and energy expenditure women with morbid obesity.

New optical technologies were developed to continuously measure cerebral blood flow (CBF) and oxygen metabolism (CMRO2) non-invasively through the skull. Methods and devices were created to improve the performance of near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS) for use in experimental animals and humans. These were employed to investigate cerebral metabolism and cerebrovascular reactivity under different states of anesthesia and during models of pathological states. Burst suppression is a brain state arising naturally in pathological conditions or under deep general anesthesia, but its mechanism and consequences are not well understood. Electroencephalography (EEG) and cortical hemodynamics were simultaneously measured in rats to evaluate the coupling between cerebral oxygen metabolism and neuronal activity in the burst suppressed state. EEG bursts were used to deconvolve NIRS and DCS signals into the hemodynamic and metabolic response function for an individual burst. This response was found to be similar to the stereotypical functional hyperemia evoked by normal brain activation. Thus, spontaneous burst activity does not cause metabolic or hemodynamic dysfunction in the cortex. Furthermore, cortical metabolic activity was not associated with the initiation or termination of a burst. A novel technique, time-domain DCS (TD-DCS), was introduced to significantly increase the sensitivity of transcranial CBF measurements to the brain. A new time-correlated single photon counting (TCSPC) instrument with a custom high coherence pulsed laser source was engineered for the first-ever simultaneous measurement of photon time of flight and DCS autocorrelation decays. In this new approach, photon time tags are exploited to determine path-length-dependent autocorrelation functions. By correlating photons according to time of flight, CBF is distinguished from superficial blood flow. Experiments in phantoms and animals demonstrate TD-DCS has significantly greater sensitivity to the brain than existing transcranial techniques. Intracranial pressure (ICP) modulates both steady-state and pulsatile CBF, making CBF a potential marker for ICP. In particular, the critical closing pressure (CrCP) has been proposed as a surrogate measure of ICP. A new DCS device was developed to measure pulsatile CBF non-invasively. A novel method for estimating CrCP and ICP from DCS measurement of pulsatile microvascular blood flow in the cerebral cortex was demonstrated in rats. / 2018-03-08T00:00:00Z

PURPOSE: Pregnancy is a physically impactful process in a woman’s life. During this time, a woman will gain weight and research has shown that many women will retain some extra weight after delivery. Because of this, recovery in the postpartum period is pivotal to avoiding the implications of weight retention. The postpartum period is vastly understudied in both the research and medical communities and this gap between pregnancy and postpartum research needs to be bridged. Therefore, the purpose of this study was to investigate metabolic changes from pregnancy to postpartum and to study how factors such as sleep and breastfeeding can impact metabolic values in the postpartum period. METHODS: Women participated in a pregnancy study visit at 32-34 weeks of gestation (n = 25) and attended two subsequent visits at 4-6 months (n = 25) and 12-13 months postpartum (n = 16). At these visits, the women had a baseline blood draw and baseline metabolic measurements taken via indirect calorimetry. At the pregnancy visit, participants completed a demographic survey and a dietary questionnaire (DHQ-II). At the postpartum visits, they completed the same surveys, along with validated sleep and breastfeeding surveys. RESULTS: Absolute resting metabolic rate (RMR) was significantly higher during pregnancy than at 4-6 months postpartum and 12-13 months postpartum (p < 0.001 and p = 0.001, respectively). Accounting for body weight, relative RMR was significantly higher during pregnancy than at 4-6 months postpartum. With regard to sleep, women deemed to be “good sleepers” had a significantly higher relative RMR than those who were deemed “poor sleepers” (23.6 ± 2.5 vs 20.8 ± 2.3, p = 0.009). With regard to breastfeeding, women who breastfed had a relative RMR than the women who did not breastfeed (22.8 ± 2.6 vs 20.4 ± 2.3, p = 0.046). CONCLUSIONS: There are hypermetabolic changes that take place during pregnancy. These values seem to decrease into the postpartum period. Women who demonstrate an improved sleep quality and who opt to breastfeed tend to have improved metabolic responses. This could help combat the struggle with postpartum weight retention that some women face.

L'objectif de cette thèse était de faire un bilan des méthodes et outils validés chez les patients DT2 et de développer une méthode d'estimation de la DE précise et adaptée à ces patients. Après avoir défini les activités quotidiennes les plus couramment réalisées dans une population de patients DT2 (Étude 1), nous nous sommes intéressés aux activités statiques et à la marche. Notre seconde étude a montré que le coût énergétique brut et net lors de la marche est respectivement 8,7 et 14,3 % plus élevé chez les patients DT2 en comparaison à un groupe témoin. Ce résultat mettait en avant la nécessité de valider une méthode d'estimation de la DE adaptée aux spécificités de la population diabétique. Les résultats de notre troisième étude ont démontré la validité de la DE estimée à partir d'un capteur intelligent et d'un algorithme existant pour différentes positions statiques et vitesses de marche chez des sujets DT2 et témoins. Enfin, dans une quatrième étude, trois équations d'estimation de la DE totale ont été développées à partir des données d'accélérations issues de trois capteurs intelligents (bas du dos, hanche et cheville) pour une population de sujets DT2 et témoins. Ces trois équations permettent d'estimer une DE totale lors d'activités statiques et de marches avec une différence moyenne respectivement de 0,009, -0,007 et -0,008 kcal/min pour le bas du dos, la hanche et la cheville en comparaison à celle de référence. Ainsi, ce travail de thèse a permis de valider trois équations d’estimation de la DE totale adaptés à une population de patients DT2, normo-pondérés ou en surpoids et âgés de 35 à 80 ans, basés sur les données d'un capteur intelligent. / The aim of this thesis is to review the methods and tools validated in T2D patients and to developed precise and adapted EE estimation method for these patients. After defining the most common daily activity in T2D patients (Study 1), we are interested, in particular, on static activities and walking. The results of our second study showed that the gross and net metabolic rate were 8.7 % and 14.3 % higher in T2D patients than in control subjects, respectively. These results highlight the need to validate an EE estimation method, adapted to diabetic’s specificities. The results of our third study demonstrated the validity of the activity-related EE estimated with a smart sensor and a validated algorithm during static activities and walking in T2D patients and healthy subjects. However, our results showed a lower accuracy of the estimated EE during walking in T2D patients in comparison with healthy subjects. Finally, in a fourth study, three equations estimating the total EE have been developed with acceleration data from three smart sensors (lower back, hip and ankle) and personal data (body mass index, sex, diabetes) from T2D and healthy subjects. These three equations allow to estimate the total EE during static activities and walking with a mean bias of 0.009, -0.007 et -0.008 kcal/min for the lower back, hip and ankle equation, respectively, in comparison with the reference value. Thus, this thesis enables to validate three suitable equations for the estimation of total EE in population including healthy and T2D patients, normal-weighted and overweighed and aged between 35 and 80 years, based on data from a smart sensor.

Energy intake (EI) and energy expenditure (EE) across the menstrual cycle (MC), while considering body adiposity, have not been previously evaluated in the same individuals. This study mainly examined the variations in energy balance (EB) across MC. Seventeen women (Body fat-DXA:28.5%) participated in three identical sessions during distinct phases of the MC: Early-follicular, Late-follicular/ovulation and Mid-luteal (confirmed by basal temperature and sex-steroid hormones). EI, resting metabolic rate (RMR), physical-activity EE (PAEE), severity of PMS, leptin and relative-reinforcing value (RRV) of preferred foods were measured during each phase. No differences in body fat, EI, RMR, PAEE, leptin and RRV of food were noted across MC. Trends were noted in preferred snack (p=0.06) and combined snack/fruit (p=0.06) intakes, while differences were noted in severity of PMS (p<0.05) across phases. Changes in EB across the MC were not noted. PMS was more severe, and preferred snack and combined snack/fruit intakes were slightly higher during mid-luteal phase.

<p>The rationale of this study is to apply light stable isotope chemistry towards investigations that require temporally high-resolution data. High-resolution (or high sampling frequency) data sets, are critical for testing environmental and/or paleoenvironmental hypotheses that seek to explain processes occurring over rapid or short time intervals. The investigation of climate variation (e.g., seasonality, El Niño, deglaciation), animal migration and physiology, and disturbance ecology (e.g., fire, flooding) benefits from the recovery of proxy information at decadal to subannual resolutions. The type of material used also dictates a spatial scale. Herein are presented four studies that utilize high-resolution light stable isotope profiles with contrasting temporal and spatial scales. The first study employs advances in three-dimensional computer-controlled micromilling to recover ~daily to weekly deposited carbonate from small (~1 cm) mollusc shells. Stable oxygen isotope values from freshwater mollusc shells are predictably related to the local environment of growth using previously published temperature-fractionation relationships, providing a paleoclimate record of temperature and precipitation. The second study investigates variation in stable carbon isotope values from Aplodinotus grunniens otoliths, for which high-resolution patterns were critical in assessing metabolic rate as the governing control. The third study employs high-resolution stable oxygen and carbon isotope values to determine chinook salmon (Oncorhynchus tshawytscha) seasonal and ontogenetic migration in Lake Ontario and its tributaries. Lastly, high-resolution stable hydrogen and carbon isotope values of chitin derived from Mexican free-tailed bat (Tadarida brasiliensis) guano are presented, providing a record of abrupt climate change. Thus, this thesis reports on promising new research avenues for paleoclimatology, paleoecology, and modern ecology.

Energy intake (EI) and energy expenditure (EE) across the menstrual cycle (MC), while considering body adiposity, have not been previously evaluated in the same individuals. This study mainly examined the variations in energy balance (EB) across MC. Seventeen women (Body fat-DXA:28.5%) participated in three identical sessions during distinct phases of the MC: Early-follicular, Late-follicular/ovulation and Mid-luteal (confirmed by basal temperature and sex-steroid hormones). EI, resting metabolic rate (RMR), physical-activity EE (PAEE), severity of PMS, leptin and relative-reinforcing value (RRV) of preferred foods were measured during each phase. No differences in body fat, EI, RMR, PAEE, leptin and RRV of food were noted across MC. Trends were noted in preferred snack (p=0.06) and combined snack/fruit (p=0.06) intakes, while differences were noted in severity of PMS (p<0.05) across phases. Changes in EB across the MC were not noted. PMS was more severe, and preferred snack and combined snack/fruit intakes were slightly higher during mid-luteal phase.

Objective: The aim of this study was to compare equations used to calculate BMR to values of BMR obtained from measurements in order to determine the most suitable equation to be used on children and adolescents with CF. Design: The participants where children and adolescents with CF. Data was collected from the division of Clinical Nutrition at Uppsala Akademiska Sjukhus. Age, weight, height, BMI, BMR, FFM and FM was recorded from 27 measurements. BMR from the participants collected from the indirect respiratory calorimetry was compared to the results obtained from five equations used to obtain a calculated value of BMR. Results: Tverskayas equation was best correlated with the measured BMR for the whole group. The equation underestimated BMR for the participants with a measured BMR over 1400 kcal/24h and overestimated BMR for participants with a measured BMR under 1400 kcal/24h. Similar results could be seen in the subgroups boys, girls and adolescents. Maffeis equation can be applied on the subgroup children. However, larger studies are needed to guarantee the results. Conclusion: It is desirable that an equation for calculating BMR would be developed that is specifically developed for children and adolescents with a low to normal BMI that takes into consideration a heightened metabolism and is therefore suitable for children and adolescents with CF. / Syfte: Att utifrån uppmätt BMR jämföra olika ekvationer för att hitta den mest lämpliga ekvationen för beräknandet av ett förutsätt värde av basalmetabolism hos en grupp barn och ungdomar med cystisk fibros. Metod: Deltagarna var barn och ungdomar med CF. Data till arbetet hämtades från enheten för klinisk nutrition vid Uppsala Akademiska sjukhus. Ålder, vikt, längd, BMI, BMR, FFM och FM samlades in från totalt 27 mättillfällen. Deltagarnas BMR, som uppmätts genom indirekta respiratorisk kalorimetri, jämfördes med fem ekvationer som räknar ut BMR utifrån olika antropometriska mått. Resultat: Tverskayas ekvation överensstämde bäst med uppmätt BMR i gruppen som helhet. Ekvationen underskattade dock BMR hos deltagare med ett BMR-behov över 1400 kcal/dygn och överskattade BMR hos deltagare med ett BMR-behov lägre än 1400 kcal/dygn. Liknande resultat sågs i undergrupperna pojkar, flickor och ungdomar. Maffeis ekvation skulle möjligen kunna tillämpas på gruppen barn, dock behöver större studier utföras för att kunna dra säkra slutsatser. Slutsats: Det vore önskvärt att det utvecklas en ekvation för BMR, särskilt utvecklad för barn och ungdomar med lågt till normalt BMI, som tar hänsyn till förhöjt BMR och som därmed lämpar sig särskilt för barn och ungdomar med CF.

<p>The rationale of this study is to apply light stable isotope chemistry towards investigations that require temporally high-resolution data. High-resolution (or high sampling frequency) data sets, are critical for testing environmental and/or paleoenvironmental hypotheses that seek to explain processes occurring over rapid or short time intervals. The investigation of climate variation (e.g., seasonality, El Niño, deglaciation), animal migration and physiology, and disturbance ecology (e.g., fire, flooding) benefits from the recovery of proxy information at decadal to subannual resolutions. The type of material used also dictates a spatial scale. Herein are presented four studies that utilize high-resolution light stable isotope profiles with contrasting temporal and spatial scales. The first study employs advances in three-dimensional computer-controlled micromilling to recover ~daily to weekly deposited carbonate from small (~1 cm) mollusc shells. Stable oxygen isotope values from freshwater mollusc shells are predictably related to the local environment of growth using previously published temperature-fractionation relationships, providing a paleoclimate record of temperature and precipitation. The second study investigates variation in stable carbon isotope values from Aplodinotus grunniens otoliths, for which high-resolution patterns were critical in assessing metabolic rate as the governing control. The third study employs high-resolution stable oxygen and carbon isotope values to determine chinook salmon (Oncorhynchus tshawytscha) seasonal and ontogenetic migration in Lake Ontario and its tributaries. Lastly, high-resolution stable hydrogen and carbon isotope values of chitin derived from Mexican free-tailed bat (Tadarida brasiliensis) guano are presented, providing a record of abrupt climate change. Thus, this thesis reports on promising new research avenues for paleoclimatology, paleoecology, and modern ecology.

Human thermal environments constitute complex combinations of various interacting thermal factors. The transient and non-uniform nature of those thermal factors further increases the complexity of the thermal comfort problem. The conventional approach to the thermal comfort problem has been simplifying the problem and providing steady thermal environments which would satisfy the majority of the people in a given space. However, several problems emerged with this approach. People became finely tuned to the narrow range of conditions and developed expectations for the same conditions which made them uncomfortable when there were slight deviations from those conditions. Also, the steady approach didn't solve the comfort problem because, in practice, people move between spaces, and thermal conditions such as metabolic rate, surface temperatures, airflow speed and direction vary in a typical day. A human subject test was designed to determine the transient relationship between the people and their environments. In the first part, thermal perceptions of people were taken during various metabolic rate conditions. In the second and the third parts, transient conditions of different thermal factors were created. Various combinations of airflow frequencies, airflow location around the body, metabolic rate, and room temperatures were tested for their individual and interaction effects of providing thermal comfort. The concept of Localized Dynamic Airflow was proposed in which room airflow was simply redirected to different parts of the body with a varying airflow speed. Results showed that males and females respond differently to the thermal conditions. The room temperatures they found neutral were significantly different. People‟s thermal comfort during transient metabolic conditions was similar to high metabolic conditions. This heightened response extended into the next ten minutes after the high metabolic conditions ended. Test results suggested that people tolerate higher temperatures during transient environmental conditions. The average response was for comfortable even during the high temperature (83°F) and high metabolic rate (4 met) conditions. Low energy use of the localized dynamic airflow and the increased room temperatures has significant potential for monetary savings.