In this thesis, we have addressed two key objectives: 1) to gain more insight in various pathophysiological aspects of cardiometabolic diseases including in the disease proneSouth Asian population,... Show moreIn this thesis, we have addressed two key objectives: 1) to gain more insight in various pathophysiological aspects of cardiometabolic diseases including in the disease proneSouth Asian population, and 2) to study the physiological effects of cold exposure and identify a novel pharmacological approach to directly target BAT. Show less
Where people live and work together it is not always possible to modify the ambient temperature; ways must therefore be found that allow individuals to feel thermally comfortable in such settings.... Show moreWhere people live and work together it is not always possible to modify the ambient temperature; ways must therefore be found that allow individuals to feel thermally comfortable in such settings. The Embr Wave (R) is a wrist-worn device marketed as a 'personal thermostat' that can apply a local cooling stimulus to the skin. The aim of the present study was to determine the effect of an intermittent mild cold stimulus of 25 degrees C for 15-20 s every 5 min over 3.5 days under free-living conditions on 1) skin temperature, 2) perception of skin temperature, 3) sleep quality and 4) resting energy expenditure (REE) in young, healthy adults. Ten subjects wore the device for 3.5 consecutive days. This intervention reduced distal skin temperature after correcting for personal ambient temperature (P < 0.05), but did not affect the subjects' the perception of skin temperature, sleep quality or REE (all P >= 0.051). Thus, this intermittent mild cold regime can reduce distal skin temperature, and wearing it under free-living conditions for 3.5 days does not seem to impair the perception of skin temperature and sleep quality or modify REE. Show less
Purpose Nowadays, 2-deoxy-2-[F-18]fluoro-D-glucose ([F-18]FDG) positron emission tomography (PET)/X-ray computed tomography (CT) is considered the best available technique to in vivo determination... Show morePurpose Nowadays, 2-deoxy-2-[F-18]fluoro-D-glucose ([F-18]FDG) positron emission tomography (PET)/X-ray computed tomography (CT) is considered the best available technique to in vivo determination of human BAT volume. The most used Hounsfield unit (HU) threshold for BAT quantification is from - 250 to - 50 HU. Therefore, the main objective of the present study is (i) to examine the influence of SUV and HU thresholds on BAT quantification by [F-18]FDG-PET/CT scan, (ii) to identify the proportion of BAT which is not detected by [F-18]FDG-PET/CT scan when limiting the range between - 10 and - 50 HU, and (iii) to describe the distribution of BAT radiodensity by weight status and sex in young healthy individuals. Procedures We measured 125 individuals after a personalized cooling protocol with a static [F-18]FDG-PET/CT scan. We quantified BAT using different combination of threshold in every single HU for all participants. Results We observed that the SUV threshold influences BAT quantification by [F-18]FDG-PET/CT scans more than the HU range. We found that the range from - 50 to - 10 HU had the highest proportion of total BAT volume (43.2 %), which represents 41.4 % of the total BAT metabolic activity in our cohort. We also observed that BAT volume was not different between categories of body mass index, as well as BAT activity (SUVmean). In addition, BAT was less dense in women than in men, although the BAT activity (SUVmean) was higher in all ranges of HU. We also observed that the radiodensity of BAT located in the cervical area was mainly in the range from - 50 to - 10 HU. Conclusion Therefore, all future human studies using static [F-18]FDG-PET/CT scans should include BAT in the radiodensity range from - 50 to - 10 HU. Show less
Rozendaal, Y.J.W.; Wang, Y.N.; Hilbers, P.A.J.; Riel, N.A.W. van 2019
BackgroundA positive energy balance is considered to be the primary cause of the development of obesity-related diseases. Treatment often consists of a combination of reducing energy intake and... Show moreBackgroundA positive energy balance is considered to be the primary cause of the development of obesity-related diseases. Treatment often consists of a combination of reducing energy intake and increasing energy expenditure. Here we use an existing computational modelling framework describing the long-term development of Metabolic Syndrome (MetS) in APOE3L.CETP mice fed a high-fat diet containing cholesterol with a human-like metabolic system. This model was used to analyze energy expenditure and energy balance in a large set of individual model realizations.ResultsWe developed and applied a strategy to select specific individual models for a detailed analysis of heterogeneity in energy metabolism. Models were stratified based on energy expenditure. A substantial surplus of energy was found to be present during MetS development, which explains the weight gain during MetS development. In the majority of the models, energy was mainly expended in the peripheral tissues, but also distinctly different subgroups were identified.In silico perturbation of the system to induce increased peripheral energy expenditure implied changes in lipid metabolism, but not in carbohydrate metabolism. In silico analysis provided predictions for which individual models increase of peripheral energy expenditure would be an effective treatment.ConclusionThe computational analysis confirmed that the energy imbalance plays an important role in the development of obesity. Furthermore, the model is capable to predict whether an increase in peripheral energy expenditure - for instance by cold exposure to activate brown adipose tissue (BAT) - could resolve MetS symptoms. Show less
