AbstractChronic excessive activation of glucocorticoid receptors induces obesity, insulin resistance, glucose intolerance, dyslipidaemia and hypertension. Subtle abnormalities of the ...hypothalamic–pituitary–adrenal axis and/or of tissue sensitivity to glucocorticoids are also associated with these cardiovascular risk factors in patients with the metabolic syndrome. Furthermore, glucocorticoids have direct effects on the heart and blood vessels, mediated by both glucocorticoid and mineralocorticoid receptors and modified by local metabolism of glucocorticoids by the 11β-hydroxysteroid dehydrogenase enzymes. These effects influence vascular function, atherogenesis and vascular remodelling following intra-vascular injury or ischaemia. This article reviews the systemic and cardiovascular effects of glucocorticoids, and the evidence that glucocorticoids not only promote the incidence and progression of atherogenesis but also modify the recovery from occlusive vascular events and intravascular injury. The conclusion is that manipulation of glucocorticoid action within metabolic and cardiovascular tissues may provide novel therapeutic avenues to combat cardiovascular disease.
The discovery of brown adipose tissue (BAT) in adult humans presents a new therapeutic target for metabolic disease; however, little is known about the regulation of human BAT. Chronic glucocorticoid ...excess causes obesity in humans, and glucocorticoids suppress BAT activation in rodents. We tested whether glucocorticoids regulate BAT activity in humans. In vivo, the glucocorticoid prednisolone acutely increased 18fluorodeoxyglucose uptake by BAT (measured using PET/CT) in lean healthy men during mild cold exposure (16°C–17°C). In addition, prednisolone increased supraclavicular skin temperature (measured using infrared thermography) and energy expenditure during cold, but not warm, exposure in lean subjects. In vitro, glucocorticoids increased isoprenaline-stimulated respiration and UCP-1 in human primary brown adipocytes, but substantially decreased isoprenaline-stimulated respiration and UCP-1 in primary murine brown and beige adipocytes. The highly species-specific regulation of BAT function by glucocorticoids may have important implications for the translation of novel treatments to activate BAT to improve metabolic health.
Display omitted
•Glucocorticoids acutely increase but chronically suppress BAT activity in humans•Glucocorticoids increase UCP-1 and respiration in human brown adipocytes•Glucocorticoids decrease UCP-1 and respiration in murine brown and beige adipocytes•Species-specific differences exist in the regulation of BAT activation
The regulation of brown adipose tissue (BAT) in humans is not well understood. Ramage et al. show that glucocorticoids acutely increase BAT in vivo and in vitro in humans through increasing UCP-1. However, glucocorticoids decrease UCP-1 in murine beige/ brown adipocytes, identifying species-specific differences in the regulation of BAT function.
Student satisfaction is important in the evaluation of distance education courses as it is related to the quality of online programs and student performance. Interaction is a critical indicator of ...student satisfaction; however, its impact has not been tested in the context of other critical student- and class-level predictors. In this study, we tested a regression model for student satisfaction involving student characteristics (three types of interaction, Internet self-efficacy, and self-regulated learning) and class-level predictors (course category and academic program). Data were collected in a sample of 221 graduate and undergraduate students responding to an online survey. The regression model was tested using hierarchical linear modeling (HLM). Learner–instructor interaction and learner–content interaction were significant predictors of student satisfaction but learner–learner interaction was not. Learner–content interaction was the strongest predictor. Academic program category moderated the effect of learner–content interaction on student satisfaction. The effect of learner–content interaction on student satisfaction was stronger in Instructional Technology and Learning Sciences than in psychology, physical education or family, consumer, and human development. In sum, the results suggest that improvements in learner–content interaction yield most promise in enhancing student satisfaction and that learner–learner interaction may be negligible in online course settings.
•HLM is applied to test a predictive model for student satisfaction.•Level-1 variables include interaction, Internet self-efficacy, and self-regulation.•Level-2 predictors include course category and program.•Hierarchical linear modeling is utilized including level-1 and level-2 variables.•Learner-content interaction is found to be the strongest predictor of satisfaction.•Program moderates the effect of learner-content interaction on satisfaction.
Fuelled by the obesity epidemic, there is considerable interest in the developmental origins of white adipose tissue (WAT) and the stem and progenitor cells from which it arises. Whereas increased ...visceral fat mass is associated with metabolic dysfunction, increased subcutaneous WAT is protective. There are six visceral fat depots: perirenal, gonadal, epicardial, retroperitoneal, omental and mesenteric, and it is a subject of much debate whether these have a common developmental origin and whether this differs from that for subcutaneous WAT. Here we show that all six visceral WAT depots receive a significant contribution from cells expressing Wt1 late in gestation. Conversely, no subcutaneous WAT or brown adipose tissue arises from Wt1-expressing cells. Postnatally, a subset of visceral WAT continues to arise from Wt1-expressing cells, consistent with the finding that Wt1 marks a proportion of cell populations enriched in WAT progenitors. We show that all visceral fat depots have a mesothelial layer like the visceral organs with which they are associated, and provide several lines of evidence that Wt1-expressing mesothelium can produce adipocytes. These results reveal a major ontogenetic difference between visceral and subcutaneous WAT, and pinpoint the lateral plate mesoderm as a major source of visceral WAT. They also support the notion that visceral WAT progenitors are heterogeneous, and suggest that mesothelium is a source of adipocytes.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Computer-based scaffolding assists students as they generate solutions to complex problems, goals, or tasks, helping increase and integrate their higher order skills in the process. However, despite ...decades of research on scaffolding in STEM (science, technology, engineering, and mathematics) education, no existing comprehensive meta-analysis has synthesized the results of these studies. This review addresses that need by synthesizing the results of 144 experimental studies (333 outcomes) on the effects of computer-based scaffolding designed to assist the full range of STEM learners (primary through adult education) as they navigated ill-structured, problem-centered curricula. Results of our random effect meta-analysis (a) indicate that computer-based scaffolding showed a consistently positive (ḡ = 0.46) effect on cognitive outcomes across various contexts of use, scaffolding characteristics, and levels of assessment and (b) shed light on many scaffolding debates, including the roles of customization (i.e., fading and adding) and context-specific support. Specifically, scaffolding's influence on cognitive outcomes did not vary on the basis of context-specificity, presence or absence of scaffolding change, and logic by which scaffolding change is implemented. Scaffolding's influence was greatest when measured at the principles level and among adult learners. Still scaffolding's effect was substantial and significantly greater than zero across all age groups and assessment levels. These results suggest that scaffolding is a highly effective intervention across levels of different characteristics and can largely be designed in many different ways while still being highly effective.
Computer-based scaffolding plays a pivotal role in improving students' higher-order skills in the context of problem-based learning for Science, Technology, Engineering and Mathematics (STEM) ...education. The effectiveness of computer-based scaffolding has been demonstrated through traditional meta-analyses. However, traditional meta-analyses suffer from small-study effects and a lack of studies covering certain characteristics. This research investigates the effectiveness of computer-based scaffolding in the context of problem-based learning for STEM education through Bayesian meta-analysis (BMA). Specifically, several types of prior distribution information inform Bayesian simulations of studies, and this generates accurate effect size estimates of six moderators (total 24 subcategories) related to the characteristics of computer-based scaffolding and the context of scaffolding utilization. The results of BMA indicated that computer-based scaffolding significantly impacted (g = 0.385) cognitive outcomes in problem-based learning in STEM education. Moreover, according to the characteristics and the context of use of scaffolding, the effects of computer-based scaffolding varied with a range of small to moderate values. The result of the BMA contributes to an enhanced understanding of the effect of computer-based scaffolding within problem-based learning.
Inhibition of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) has been proposed as a novel therapeutic target for the treatment of type 2 diabetes mellitus. Over 170 new compounds ...targeting 11β-HSD1 have been developed. This article reviews the current published literature on compounds that have reached phase II clinical trials in patients with type 2 diabetes, and summarises the preclinical evidence that such agents may be useful for associated conditions, including peripheral vascular disease, coronary artery disease and cognitive decline. In clinical trials, 11β-HSD1 inhibitors have been well tolerated and have improved glycaemic control, lipid profile and blood pressure, and induced modest weight loss. The magnitude of the effects are small relative to other agents, so that further development of 11β-HSD1 inhibitors for the primary therapeutic indication of type 2 diabetes has stalled. Ongoing programmes are focused on additional benefits for cognitive function and other cardiovascular risk factors.
Inhibition of the enzyme 11 s-hydroxysteroid dehydrogenase type 1 (lls-HSDl) has been proposed as a novel therapeutic target for the treatment of type 2 diabetes mellitus. Over 170 new compounds ...targeting lls-HSDl have been developed. This article reviews the current published literature on compounds that have reached phase II clinical trials in patients with type 2 diabetes, and summarises the preclinical evidence that such agents may be useful for associated conditions, including peripheral vascular disease, coronary artery disease and cognitive decline. In clinical trials, lls-HSDl inhibitors have been well tolerated and have improved glycaemic control, lipid profile and blood pressure, and induced modest weight loss. The magnitude of the effects are small relative to other agents, so that further development of 11 s-HSDl inhibitors for the primary therapeutic indication of type 2 diabetes has stalled. Ongoing programmes are focused on additional benefits for cognitive function and other cardiovascular risk factors.
Glucocorticoid hormones constitute an integral component of the response to stress, and many of the manifestations of glucocorticoid excess (Cushing's syndrome) are predictable on the basis of their ...acute effects to raise blood pressure, induce insulin resistance, increase protein catabolism and elevate plasma glucose. However, it appears to be a paradox that the acute lipolytic effect of glucocorticoids is not manifest in long-term weight loss in humans. The effects of glucocorticoids on glucose metabolism are well characterised, involving impaired peripheral glucose uptake and hepatic insulin resistance, and there is mounting evidence that subtle abnormalities in glucocorticoid concentrations in the plasma and/or in tissue sensitivity to glucocorticoids are important in metabolic syndrome. The effects of glucocorticoids on fatty acid metabolism are less well understood than their influence on glucose metabolism. In this article, we review the literature describing the effects of glucocorticoids on fatty acid metabolism, with particular reference to in vivo human studies. We consider the implications for contrasting acute versus chronic effects of glucocorticoids on fat accumulation, effects in different adipose depots and the potential role of glucocorticoid signalling in the pathogenesis and therapy of metabolic syndrome.
Current understanding of in vivo human brown adipose tissue (BAT) physiology is limited by a reliance on positron emission tomography (PET)/computed tomography (CT) scanning, which has measured ...exogenous glucose and fatty acid uptake but not quantified endogenous substrate utilization by BAT. Six lean, healthy men underwent 18fluorodeoxyglucose-PET/CT scanning to localize BAT so microdialysis catheters could be inserted in supraclavicular BAT under CT guidance and in abdominal subcutaneous white adipose tissue (WAT). Arterial and dialysate samples were collected during warm (∼25°C) and cold exposure (∼17°C), and blood flow was measured by 133xenon washout. During warm conditions, there was increased glucose uptake and lactate release and decreased glycerol release by BAT compared with WAT. Cold exposure increased blood flow, glycerol release, and glucose and glutamate uptake only by BAT. This novel use of microdialysis reveals that human BAT is metabolically active during warm conditions. BAT activation substantially increases local lipolysis but also utilization of other substrates such as glutamate.
Display omitted
•Human BAT shows substantial glucose uptake and lactate release during warm conditions•Glycerol recycling occurs in human BAT, and cold exposure activates BAT lipolysis•BAT uses substrates other than just glucose or fatty acids during cold activation•Microdialysis is a novel technique to measure in vivo human BAT physiology
Weir et al., using microdialysis, have shown that human brown adipose tissue (BAT) is metabolically active in warm conditions, with higher glucose uptake and lactate release than white AT. Cold activation increased glucose and glutamate uptake and glycerol release by BAT, quantifying substrate utilization and hydrolysis of BAT triglycerides during thermogenesis.
PDF
