mTORC2 sustains thermogenesis via Akt-induced glucose uptake and glycolysis in brown adipose tissue

Activation of non-shivering thermogenesis (NST) in brown adipose tissue (BAT) has been proposed as an anti-obesity treatment. Moreover, cold-induced glucose uptake could normalize blood glucose levels in insulin-resistant patients. It is therefore important to identify novel regulators of NST and cold-induced glucose uptake. Mammalian target of rapamycin complex 2 (mTORC2) mediates insulin-stimulated glucose uptake in metabolic tissues, but its role in NST is unknown. We show that mTORC2 is activated in brown adipocytes upon β-adrenergic stimulation. Furthermore, mice lacking mTORC2 specifically in adipose tissue (AdRiKO mice) are hypothermic, display increased sensitivity to cold, and show impaired cold-induced glucose uptake and glycolysis. Restoration of glucose uptake in BAT by overexpression of hexokinase II or activated Akt2 was sufficient to increase body temperature and improve cold tolerance in AdRiKO mice. Thus, mTORC2 in BAT mediates temperature homeostasis via regulation of cold-induced glucose uptake. Our findings demonstrate the importance of glucose metabolism in temperature regulation

Cold-induced changes in gene expression in brown adipose tissue, white adipose tissue and liver

Cold exposure imposes a metabolic challenge to mammals that is met by a coordinated response in different tissues to prevent hypothermia. This study reports a transcriptomic analysis in brown adipose tissue (BAT), white adipose (WAT) and liver of mice in response to 24 h cold exposure at 8°C. Expression of 1895 genes were significantly (P<0.05) up- or down-regulated more than two fold by cold exposure in all tissues but only 5 of these genes were shared by all three tissues, and only 19, 14 and 134 genes were common between WAT and BAT, WAT and liver, and BAT and liver, respectively. We confirmed using qRT-PCR, the increased expression of a number of characteristic BAT genes during cold exposure. In both BAT and the liver, the most common direction of change in gene expression was suppression (496 genes in BAT and 590 genes in liver). Gene ontology analysis revealed for the first time significant (P<0.05) down regulation in response to cold, of genes involved in oxidoreductase activity, lipid metabolic processes and protease inhibitor activity, in both BAT and liver, but not WAT. The results reveal an unexpected importance of down regulation of cytochrome P450 gene expression and apolipoprotein, in both BAT and liver, but not WAT, in response to cold exposure. Pathway analysis suggests a model in which down regulation of the nuclear transcription factors HNF4α and PPARα in both BAT and liver may orchestrate the down regulation of genes involved in lipoprotein and steroid metabolism as well as Phase I enzymes belonging to the cytochrome P450 group in response to cold stress in mice. We propose that the response to cold stress involves decreased gene expression in a range of cellular processes in order to maximise pathways involved in heat production

School Effects on the Wellbeing of Children and Adolescents

Well-being is a multidimensional construct, with psychological, physical and social components. As theoretical basis to help understand this concept and how it relates to school, we propose the Self-Determination Theory, which contends that self-determined motivation and personality integration, growth and well-being are dependent on a healthy balance of three innate psychological needs of autonomy, relatedness and competence. Thus, current indicators involve school effects on children’s well-being, in many diverse modalities which have been explored. Some are described in this chapter, mainly: the importance of peer relationships; the benefits of friendship; the effects of schools in conjunction with some forms of family influence; the school climate in terms of safety and physical ecology; the relevance of the teacher input; the school goal structure and the implementation of cooperative learning. All these parameters have an influence in promoting optimal functioning among children and increasing their well-being by meeting the above mentioned needs. The empirical support for the importance of schools indicates significant small effects, which often translate into important real-life effects as it is admitted at present. The conclusion is that schools do make a difference in children’s peer relationships and well-being

The psychology of passion: A meta-analytical review of a decade of research on intrapersonal outcomes

It is just over a decade since Vallerand et al. (J Personal Soc Psychol 85:756–767, 2003) introduced the dualistic model of passion. In this study, we conduct a meta-analytical review of relationships between Vallerand et al’s two passions (viz. harmonious and obsessive), and intrapersonal outcomes, and test the moderating role of age, gender, domain, and culture. A systematic literature search yielded 94 studies, within which 27 criterion variables were reported. These criterion variables derived from four research areas within the intrapersonal sphere: (a) well-/ill-being, (b) motivation factors, (c) cognitive outcomes and, (d) behaviour and performance. From these areas we retrieved 1308 independent effect sizes and analysed them using random-effects models. Results showed harmonious passion positively corresponded with positive intrapersonal outcomes (e.g., positive affect, flow, performance). Obsessive passion, conversely, showed positive associations with positive and negative

Studies on the anti-obesity activity of zinc-α2-glycoprotein in the rat

OBJECTIVE: To investigate the anti-obesity effect of the adipokine zinc-a(2)-glycoprotein (ZAG) in rats and the mechanism of this effect. SUBJECTS: Mature male Wistar rats (540 ± 83 g) were administered human recombinant ZAG (50 µg per 100 g body weight given intravenously daily) for 10 days, while control animals received an equal volume of phosphate-buffered saline (PBS). RESULTS: Animals treated with ZAG showed a progressive decrease in body weight, without a decrease in food and water intake, but with a 0.4 °C rise in body temperature. Body composition analysis showed loss of adipose tissue, but an increase in lean body mass. The loss of fat was due to an increase in lipolysis as shown by a 50% elevation of plasma glycerol, accompanied by increased utilization of non-esterified fatty acids, as evidenced by the 55% decrease in plasma levels. Plasma levels of glucose and triglycerides were also reduced by 36-37% and there was increased expression of the glucose transporter 4 in both skeletal muscle and adipose tissue. Expression of the lipolytic enzymes adipose triglyceride lipase and hormone-sensitive lipase in the white adipose tissue (WAT) were increased twofold after ZAG administration. There was almost a twofold increased expression of uncoupling proteins 1 and 3 in brown adipose tissue and WAT, which would contribute to increased substrate utilization. Administration of ZAG increased ZAG expression twofold in the gastrocnemius muscle, BAT and WAT, which was probably necessary for its biological effect. CONCLUSION: These results show that ZAG produces increased lipid mobilization and utilization in the rat

Basal and stress-induced salivary testosterone variation across the menstrual cycle and linkage to motivation and muscle power

This study investigated salivary testosterone (sal-T) variation across the menstrual cycle in female athletes, at different competitive levels, and its association with motivation and neuromuscular power. Six elite and 16 non-elite female athletes were monitored on days 7 (D7), 14 (D14) and 21 (D21) across three menstrual cycles for basal sal-T concentrations and self-appraised motivation to train and compete. Two further measures were taken on D7, D14 and D21 across two menstrual cycles; (1) the sal-T response (delta change) to a physical stress test and (2) peak power (PP) response to a 6-sec cycle sprint following a post-activation potentiation (PAP) stimulus. Basal sal-T concentrations increased by 17±27% from D7 to D14 before decreasing by -25±43% on D21 (p102%) who showed larger menstrual changes. Motivation, sal-T reactivity to stress and the PP responses to a PAP stimulus also varied by testing day (p<0.05), in parallel to basal sal-T and in favour of the elite group. Furthermore, stronger within-subject relationships (p<0.001) between basal sal-T and motivation emerged in the elites (r = 0.70-0.75) versus the non-elites (r = 0.41-0.50). In conclusion, menstrual cycle changes in sal-T were more obvious in high-performing female athletes with higher sal-T concentrations. This was accompanied by greater training motivation, a more pronounced sal-T response to a physical stressor and greater neuromuscular power in the elite group. These results support observations that female athletes with higher T are more represented at elite levels of performance

The use of opioids at the end of life: the knowledge level of Dutch physicians as a potential barrier to effective pain management

<p>Abstract</p> <p>Background</p> <p>Pain is still one of the most frequently occurring symptoms at the end of life, although it can be treated satisfactorily in most cases if the physician has adequate knowledge. In the Netherlands, almost 60% of the patients with non-acute illnesses die at home where end of life care is coordinated by the general practitioner (GP); about 30% die in hospitals (cared for by clinical specialists), and about 10% in nursing homes (cared for by elderly care physicians).</p> <p>The research question of this study is: what is the level of knowledge of Dutch physicians concerning pain management and the use of opioids at the end of life?</p> <p>Methods</p> <p>A written questionnaire was sent to a random sample of physicians of specialties most often involved in end of life care in the Netherlands. The questionnaire was completed by 406 physicians, response rate 41%.</p> <p>Results</p> <p>Almost all physicians were aware of the most basal knowledge about opioids, e.g. that it is important for treatment purposes to distinguish nociceptive from neuropathic pain (97%). Approximately half of the physicians (46%) did not know that decreased renal function raises plasma concentration of morphine(-metabolites) and 34% of the clinical specialists erroneously thought opioids are the favoured drug for palliative sedation.</p> <p>Although 91% knew that opioids titrated against pain do not shorten life, 10% sometimes or often gave higher dosages than needed with the explicit aim to hasten death. About half felt sometimes or often pressured by relatives to hasten death by increasing opioiddosage.</p> <p>The large majority (83%) of physicians was interested in additional education about subjects related to the end of life, the most popular subject was opioid rotation (46%).</p> <p>Conclusions</p> <p>Although the basic knowledge of physicians was adequate, there seemed to be a lack of knowledge in several areas, which can be a barrier for good pain management at the end of life. From this study four areas emerge, in which it seems likely that an improvement can improve the quality of pain management at the end of life for many patients in the Netherlands: 1)palliative sedation; 2)expected effect of opioids on survival; and 3) opioid rotation.</p

Development and validation of the motivations for selection of medical study (MSMS) questionnaire in India

Background and Objective Understanding medical students' motivation to select medical studies is particularly salient to inform practice and policymaking in countries-such as India-where shortage of medical personnel poses crucial and chronical challenges to healthcare systems. This study aims to develop and validate a questionnaire to assess the motivation of medical students to select medical studies. Methods A Motivation for Selection of Medical Study (MSMS) questionnaire was developed using extensive literature review followed by Delphi technique. The scale consisted of 12 items, 5 measuring intrinsic dimensions of motivations and 7 measuring extrinsic dimensions. Exploratory factor analysis (EFA), confirmatory factor analysis (CFA), validity, reliability and data quality checks were conducted on a sample of 636 medical students from six medical colleges of three North Indian states. Results The MSMS questionnaire consisted of 3 factors (subscales) and 8 items. The three principal factors that emerged after EFA were the scientific factor (e.g. research opportunities and the ability to use new cutting edge technologies), the societal factor (e.g. job security) and the humanitarian factor (e.g. desire to help others). The CFA conducted showed goodnessof-fit indices supporting the 3-factor model. Conclusion The three extracted factors cut across the traditional dichotomy between intrinsic and extrinsic motivation and uncover a novel three-faceted motivation construct based on scientific factors, societal expectations and humanitarian needs. This validated instrument can be used to evaluate the motivational factors of medical students to choose medical study in India and similar settings and constitutes a powerful tool for policymakers to design measures able to increase selection of medical curricula

In-lecture learning motivation predicts students’ motivation, intention, and behaviour for after-lecture learning: Examining the trans-contextual model across universities from UK, China, and Pakistan

This paper presents a cross-cultural examination of the trans-contextual model in University education setting. The purpose of the study was to test the effect of students’ perceived autonomy support and in-lecture learning motivation on motivation, intention, and behaviour with respect to after-lecture learning via the mediation of the social cognitive variables: attitude, subjective norm, and perceived behavioural control. University students from UK, China, and Pakistan completed the questionnaires of the study variables. Results revealed that in-lecture perceived autonomy support and autonomous motivation were positively associated with autonomous motivation and intention to engage in after-lecture learning activities via the mediation of the social cognitive variables in all samples. After controlling for the effect of past behaviour, relations between intention and behaviour were only observed in the Chinese sample. In conclusion, the trans-contextual model can be applied to University education, but cultural differences appear to moderate the predictive power of the model, particularly for the intention-behaviour relationship

Conception participative et évaluation d'un serious game pour les enfants asthmatiques

International audienceThe study described in this paper highlighted the participatory design process (PD) in the context of asthma e-learning. First, we described global process to design this tool named KidBreath. Second, we evaluated in two Year 4 classes its efficacy in a motivation way, usability, disease knowledge and interests of children by their system. Results showed, in acceptance with behaviors, high level of intrinsic motivation when using KidBreath, usability and enjoyment of edutainment activities. This pilot study tends to confirm to continue with this approach with asthma kids at home.L'étude décrite dans cet article met en exergue l'intérêt d'une approche de conception participative (CP) dans le cadre d'un apprentissage en ligne sur l'asthme pour les enfants. Après avoir décrit l'ensemble de la démarche pour la conception de cet e-learning nommé KidBreath, nous évaluons dans 2 classes de CE2 son efficacité au niveau motivationnel, utilisabilité, connaissance sur la maladie et émergence de l'intérêt que les enfants y portent à travers la curiosité qui en émerge. Les résultats, probants aux comportements observés, montrent un haut niveau de motivation intrinsèque pour utiliser l'outil, un fort taux d'utilisabilité et une grande satisfaction des activités ludo-éducatives. Cette étude pilote nous confirme de continuer dans cette approche en testant le système notamment auprès des enfants asthmatiques sur du moyen terme