Discrete TrkB-expressing neurons of the dorsomedial hypothalamus regulate feeding and thermogenesis

Mutations in the TrkB neurotrophin receptor lead to profound obesity in humans, and expression of TrkB in the dorsomedial hypothalamus (DMH) is critical for maintaining energy homeostasis. However, the functional implications of TrkB-fexpressing neurons in the DMH (DMH^TrkB) on energy expenditure are unclear. Additionally, the neurocircuitry underlying the effect of DMH^TrkB neurons on energy homeostasis has not been explored. In this study, we show that activation of DMH^TrkB neurons leads to a robust increase in adaptive thermogenesis and energy expenditure without altering heart rate or blood pressure, while silencing DMH^TrkB neurons impairs thermogenesis. Furthermore, we reveal neuroanatomically and functionally distinct populations of DMH^TrkB neurons that regulate food intake or thermogenesis. Activation of DMH^TrkB neurons projecting to the raphe pallidus (RPa) stimulates thermogenesis and increased energy expenditure, whereas DMH^TrkB neurons that send collaterals to the paraventricular hypothalamus (PVH) and preoptic area (POA) inhibit feeding. Together, our findings provide evidence that DMH^TrkB neuronal activity plays an important role in regulating energy expenditure and delineate distinct neurocircuits that underly the separate effects of DMH^TrkB neuronal activity on food intake and thermogenesis.

Impairments in energy homeostasis resulting from the compound effects of overeating and sedentary lifestyles have led to a profound increase in the rate of obesity around the world (1). Therapeutic strategies aimed at combating obesity by increasing energy expenditure or decreasing appetite have commonly failed due to counterregulatory mechanisms (2) and adverse side effects on cardiovascular physiology (3–5). To achieve safe and sustained weight loss, it will be essential to understand the mechanisms that govern and coordinate discrete physiological processes that contribute to energy homeostasis.Adaptive thermogenesis is the process by which energy is converted into heat and occurs primarily in brown adipose tissue (BAT) in response to environmental cues (6). BAT has a particularly high capacity for dissipating energy from fat and thus represents an important component of energy homeostasis. The dorsomedial hypothalamus (DMH) in the brain is centrally positioned in an established thermoregulatory neurocircuit, receiving inputs from the preoptic area (POA) (7–9) and sending excitatory projections to preautonomic neurons in the raphe pallidus (RPa) (10–13) that promote sympathetic activity in BAT, leading to increased thermogenesis. Direct chemical stimulation of the DMH (14) or activation of select populations of thermogenic DMH neurons (9, 11, 12, 15) leads to increased body temperature and energy expenditure but also significantly increases heart rate and blood pressure (12, 13, 15, 16). An inability to target increased sympathetic tone specifically in BAT without affecting other target tissues has greatly hampered strategies to treat obesity by targeting thermogenesis (4, 5).In addition to its influence on energy expenditure, the DMH also represents an important brain region in the regulation of feeding (17–19). Lesioning studies support an orexigenic role for the DMH (17), which can promote food intake through inhibitory projections to either the paraventricular hypothalamus (PVH) (18) or the arcuate nucleus (ARC) (20). Despite these early findings, evidence has also emerged that demonstrates the importance of anorexigenic populations of DMH neurons (19, 21, 22). We previously established that the activity of DMH neurons expressing the neurotrophin receptor TrkB (DMH^TrkB) is important for regulating feeding, showing that activation of DMH^TrkB neurons suppresses feeding and that deletion of the TrkB-encoding Ntrk2 gene in the DMH results in hyperphagia and obesity (21). Furthermore, humans with mutations in the TrkB-encoding NTRK2 gene exhibit severe obesity and impaired thermoregulation (23). However, it is unclear whether activation of DMH^TrkB neurons has a direct influence on adaptive thermogenesis. Additionally, the neurocircuitry through which DMH^TrkB neurons govern feeding or energy expenditure is unknown.Here, we demonstrate that DMH^TrkB neuronal activity potently promotes energy expenditure by elevating thermogenesis and physical activity with a notable lack of influence on heart rate and blood pressure. We further reveal that DMH^TrkB neurons send diverging projections to the RPa or the POA and PVH to differentially regulate energy expenditure and food intake, respectively.     

Energy utilization associated with regular activity breaks and continuous physical activity: A randomized crossover trial

Aims

To quantify and compare energy utilization associated with prolonged sitting alone, or interrupted with regular activity breaks and/or an additional bout of continuous physical activity.

Self‐report use‐of‐time tools for the assessment of physical activity and sedentary behaviour in young people: systematic review

Regular physical activity and limiting extended periods of sitting are two behaviours critical for the prevention of obesity in young people. The purpose of the systematic review was to synthesize the psychometric evidence for self‐report use‐of‐time tools that assess these behaviours. Articles were retrieved that reported reliability and/or validity for use‐of‐time tools in participants aged 18 years or under. Outcome variables were physical activity, sedentary behaviour and energy expenditure. Study quality was appraised, and the results summarized narratively. Sixteen studies and six different tools were identified. The tools were the Previous Day Physical Activity Recall, the Three‐Day Physical Activity Recall, the Physical Activity Interview, the Computerized Activity Recall, the Activitygram, and the Multimedia Activity Recall for Children and Adolescents. Overall, tools indicated moderate validity compared with objective and criterion comparison methods. Generally, validity correlation coefficients were in the range of 0.30–0.40. Correlation coefficients for test–retest reliability ranged widely from 0.24 to 0.98. Conclusion: Use‐of‐time tools have indicated moderate reliability and validity for the assessment of physical activity and energy expenditure. Future research should focus on using criterion methods and on validating specifically for sedentary behaviour outcomes. Implementation of these tools for population surveillance should be considered.     

Evaluation of activity monitors in manual wheelchair users with paraplegia

Abstract

Objective: The aim of this study was to evaluate the performance of SenseWear^® (SW) and RT3 activity monitors (AMs) in estimating energy expenditure (EE) in manual wheelchair users (MWUs) with paraplegia for a variety of physical activities.

Methods: Twenty-four subjects completed four activities including resting, wheelchair propulsion, arm-ergometry exercise, and deskwork. The criterion EE was measured by a K4b2 portable metabolic cart. The EE estimated by the SW and RT3 were compared with the criterion EE by the absolute differences and absolute percentage errors. Intraclass correlations and the Bland and Altman plots were also used to assess the agreements between the two AMs and the metabolic cart. Correlations between the criterion EE and the estimated EE and sensors data from the AMs were evaluated.

Results: The EE estimation errors for the AMs varied from 24.4 to 125.8% for the SW and from 22.0 to 52.8% for the RT3. The intraclass correlation coefficients (ICCs) between the criterion EE and the EE estimated by the two AMs for each activity and all activities as a whole were considered poor with all the ICCs smaller than 0.75. Except for deskwork, the EE from the SW was more correlated to the criterion EE than the EE from the RT3.

Conclusion: The results indicate that neither of the AMs is an appropriate tool for quantifying physical activity in MWUs with paraplegia. However, the accuracy of EE estimation could be potentially improved by building new regression models based on wheelchair-related activities.     

Outpatient rehabilitation utilization and medical expenses in children aged 0–7 years with ADHD: Analyses of population-based national health insurance data

Medical costs of attention-deficit/hyperactivity disorder (ADHD) are substantial and have a large impact on the public health system. The present study presents information regarding outpatient rehabilitation care usage and medical expenditure for children with ADHD. A cross-sectional study was conducted by analyzing data from the Taiwan National Health Insurance claims database for the year 2009. A total of 6643 children aged 0–7 years with ADHD (ICD-9-CM codes 314.0x: attention deficit disorder, 314.00: attention deficit disorder without hyperactivity, or 314.01: attention-deficit disorder with hyperactivity) who had used outpatient rehabilitation care were included in the analyses. Results showed that the mean annual rehabilitation care was 22.24 visits. Among the care users, 76% of patients were male, and 24% were female. More than half of the children with ADHD had comorbid mental illnesses as well. A logistic regression analysis of outpatient rehabilitation expenditure (low vs. high) showed that of those children with ADHD, those aged 0–2 years tended to incur more medical costs than those aged 6–7 years. Other factors such as frequency of rehabilitation visits, hospital medical setting and ownership, location of medical care setting, and types of rehabilitation were also significantly correlated with medical expenditure. The results from this study suggest that health care systems should ensure accurate diagnosis and measurement of impairment to maintain appropriate and successful management of rehabilitation needs for children with ADHD.     

机械通气患儿能量代谢特点和喂养状态研究

目的：通过间接测热法测定机械通气患儿静息能量消耗,研究其能量代谢特点和喂养状态,为改进营养支持策略提供依据。方法以2013年2月至2013年11月入住PICU,符合间接测热条件的37例机械通气患儿为研究对象,自符合测定条件起第1、4、7、10、14和21天测定静息能量消耗( measurement of resting energy expenditure,MREE),运用Schofield-HTWT公式计算预测静息能量消耗值( predicted resting energy expenditure,PREE),并统计每日热量摄入值。按MREE/PREE比值评定代谢状态：低代谢(<90％)、正常代谢(90％~110％)和高代谢(>110％)。按热量摄入值/MREE 比值评定喂养状态：喂养不足(<90％)、喂养适当(90％~110％)和喂养过度(>110％)。结果37例危重症儿童机械通气第1天,15例(40.5％)为低代谢,9例(24.3％)为正常代谢,13例(35.1％)为高代谢;机械通气第7天,呈高代谢状态患儿比例增加至46.7％,但较第1天无统计学差异(χ2＝0.516,P＝0.972)。营养支持应用率为81.1％;实施营养支持者,累计实施间接测热82次,每日热量摄入值为(33.4±22.2)kcal/(kg?d),显著低于MREE水平[(53.7±17.4)kcal/(kg?d)](t＝6.505,P<0.01)。在实施营养支持过程中,机械通气患儿有62 d(75.6％)喂养不足,8 d(9.8％)喂养适当,12 d(14.6％)喂养过度。结论 PICU滞留期间机械通气患儿能量代谢状态不断变化,且PICU滞留期间有近90％的时间里患儿喂养不达标。