Hypocretin/orexin in fish physiology with emphasis on zebrafish

One hypocretin/orexin (hcrt) gene has been identified in several fish species. The first pufferfish gene was identified in 2002 and the zebrafish gene was cloned in 2004. Its structure is very similar to that of mammals, and it encodes for two active peptides with C-termini similar to those of mammals. The gene is expressed in the brain in only one hypothalamic nucleus, which sends projections to the telencephalon, diencephalon, mesencephalon and rhombencephalon. The terminal fibres are found in close contact with many aminergic cell groups, including those of raphe serotonergic, locus coeruleus noradrenergic, several dopaminergic cell groups and the sole histaminergic hypothalamic cluster. One receptor corresponding to mammalian hcrt 2 receptor has been identified in fish. Overexpression of hcrt in zebrafish has been reported to consolidate wakefulness and inhibit rest. On the other hand, fish lacking the hcrt receptor show short and fragmented sleep instead of sleepiness and cataplexy. Food deprivation increases hcrt mRNA expression in zebrafish brain, and intracerebroventricular hcrt peptides stimulate food consumption and feeding behaviour in goldfish. Hcrt peptides thus have important roles in fish physiology. Many genetic and functional methods available render fish, especially zebrafish, a suitable organism to study new aspects of hcrt physiology in vertebrates.     

Hypocretin/orexin and narcolepsy: new basic and clinical insights

Narcolepsy is a chronic sleep disorder, characterized by excessive daytime sleepiness (EDS), cataplexy, sleep paralysis and hypnagogic hallucinations. Both sporadic (95%) and familial (5%) forms of narcolepsy exist in humans. The major pathophysiology of human narcolepsy has been recently discovered based on the discovery of narcolepsy genes in animals; the genes involved in the pathology of the hypocretin/orexin ligand and its receptor. Mutations in hypocretin-related genes are rare in humans, but hypocretin ligand deficiency is found in a large majority of narcolepsy with cataplexy. Hypocretin ligand deficiency in human narcolepsy is probably due to the post-natal cell death of hypocretin neurones. Although a close association between human leucocyte antigen (HLA) and human narcolepsy with cataplexy suggests an involvement of autoimmune mechanisms, this has not yet been proved. Hypocretin deficiency is also found in symptomatic cases of narcolepsy and EDS with various neurological conditions, including immune-mediated neurological disorders, such as Guillain–Barre syndrome, MA2-positive paraneoplastic syndrome and neuromyelitis optica (NMO)-related disorder. The findings in symptomatic narcoleptic cases may have significant clinical relevance to the understanding of the mechanisms of hypocretin cell death and choice of treatment option. The discoveries in human cases lead to the establishment of the new diagnostic test of narcolepsy (i.e. low cerebrospinal fluid hypocretin-1 levels for ‘narcolepsy with cataplexy’ and ‘narcolepsy due to medical condition’). As a large majority of human narcolepsy patients are ligand deficient, hypocretin replacement therapy may be a promising new therapeutic option, and animal experiments using gene therapy and cell transplantations are in progress.     

人体运动量及能耗的测量方法

正确评价人体运动量是研究运动与健康、训练与训练效率之间关系的关键。近几十年来 ,研究者们一直在寻找一种能客观、准确、可靠评估人体运动的方法。近几年出现的基于加速度计的运动数据处理装置为评估人体运动提供了新的思路和实际方法。本文对近年来这方面的研究进展作了一个较为详细的综述。并对基于三维加速度计的新型人体运动数据处理装置应用于评估人体运动的原理和具体方法进行了介绍。     

Impact of EPOC adjustment on estimation of energy expenditure using activity monitors

Purpose: To examine the accuracy of activity monitors in estimating energy expenditure (EE) during activities of varying mode and intensity and to evaluate the impact of including energy expended during recovery from activity (EPOC) on the EE estimate. EE estimates obtained from the Fitbit Surge (FBS), Garmin Vívofit (GV) and SenseWear Armband Mini (SWA) were compared to criterion EE with and without EPOC adjustments during moderate- and vigorous-intensity treadmill and cycling activities.

Methods: Participants (N?=?34; 23 males) completed counterbalanced treadmill or cycling conditions, comprised of a resting metabolic rate measurement, 10-min bouts of moderate- and vigorous-intensity activity and an EPOC measurement. Participants simultaneously wore the three activity monitors and a portable metabolic analyser.

Results: The FBS provided lowest percent error (PE) during treadmill walking (4.4%) and the GV during moderate (6.4%) and vigorous (?0.1%) cycling bouts. EPOC-adjusted PE was higher than non-EPOC PE across all monitors and activities. Mean absolute error rate (MAPE), indicating overall measurement error, was the smallest for the FBS (14.1%) during moderate treadmill walking and the largest for the SWA (53.5%) for vigorous intensity cycling. Only the FBS had comparable non-EPOC (14.6%) and EPOC-adjusted (17.6%) MAPE during treadmill walking.

Conclusion: The activity monitors tended to underestimate EE during moderate and vigorous treadmill and cycling activities. The EE estimates from the activity monitors did not account for the energy cost met by anaerobic means during activity, as suggested by the higher EPOC-adjusted EE error rates.     

Hypocretin (orexin) loss in Alzheimer's disease

Sleep disturbances in Alzheimer's disease (AD) patients are associated with the severity of dementia and are often the primary reason for institutionalization. These sleep problems partly resemble core symptoms of narcolepsy, a sleep disorder caused by a general loss of the neurotransmitter hypocretin. AD is a neurodegenerative disorder targeting different brain areas and types of neurons. In this study, we assessed whether the neurodegenerative process of AD also affects hypothalamic hypocretin/orexin neurons. The total number of hypocretin-1 immunoreactive neurons was quantified in postmortem hypothalami of AD patients (n = 10) and matched controls (n = 10). In addition, the hypocretin-1 concentration was measured in postmortem ventricular cerebrospinal fluid of 24 AD patients and 25 controls (including the patients and controls in which the hypothalamic cell counts were performed). The number of hypocretin-1 immunoreactive neurons was significantly decreased by 40% in AD patients (median [25th-75th percentiles]); AD 12,935 neurons (9972-19,051); controls 21,002 neurons (16,439-25,765); p = 0.049). Lower cerebrospinal fluid (CSF) hypocretin-1 levels were found in AD patients compared with controls (AD: 275 pg/mL [197-317]; controls: 320 pg/mL [262-363]; p = 0.038). Two AD patients with documented excessive daytime sleepiness showed the lowest CSF hypocretin-1 concentrations (55 pg/mL and 76 pg/mL). We conclude that the hypocretin system is affected in advanced AD. This is reflected in a 40% decreased cell number, and 14% lower CSF hypocretin-1 levels.     

Hypocretin/orexin antagonism enhances sleep-related adenosine and GABA neurotransmission in rat basal forebrain

Hypocretin/orexin (HCRT) neurons provide excitatory input to wake-promoting brain regions including the basal forebrain (BF). The dual HCRT receptor antagonist almorexant (ALM) decreases waking and increases sleep. We hypothesized that HCRT antagonists induce sleep, in part, through disfacilitation of BF neurons; consequently, ALM should have reduced efficacy in BF-lesioned (BFx) animals. To test this hypothesis, rats were given bilateral IgG-192-saporin injections, which predominantly targets cholinergic BF neurons. BFx and intact rats were then given oral ALM, the benzodiazepine agonist zolpidem (ZOL) or vehicle (VEH) at lights-out. ALM was less effective than ZOL at inducing sleep in BFx rats compared to controls. BF adenosine (ADO), γ-amino-butyric acid (GABA), and glutamate levels were then determined via microdialysis from intact, freely behaving rats following oral ALM, ZOL or VEH. ALM increased BF ADO and GABA levels during waking and mixed vigilance states, and preserved sleep-associated increases in GABA under low and high sleep pressure conditions. ALM infusion into the BF also enhanced cortical ADO release, demonstrating that HCRT input is critical for ADO signaling in the BF. In contrast, oral ZOL and BF-infused ZOL had no effect on ADO levels in either BF or cortex. ALM increased BF ADO (an endogenous sleep-promoting substance) and GABA (which is increased during normal sleep), and required an intact BF for maximal efficacy, whereas ZOL blocked sleep-associated BF GABA release, and required no functional contribution from the BF to induce sleep. ALM thus induces sleep by facilitating the neural mechanisms underlying the normal transition to sleep.     

Comparison of steps and energy expenditure assessment in adults of Fitbit Tracker and Ultra to the Actical and indirect calorimetry

Abstract

Epidemic levels of inactivity are associated with chronic diseases and rising healthcare costs. To address this, accelerometers have been used to track levels of activity. The Fitbit and Fitbit Ultra are some of the newest commercially available accelerometers. The purpose of this study was to determine the reliability and validity of the Fitbit and Fitbit Ultra. Twenty-three subjects were fitted with two Fitbit and Fitbit Ultra accelerometers, two industry-standard accelerometers and an indirect calorimetry device. Subjects participated in 6-min bouts of treadmill walking, jogging and stair stepping. Results indicate the Fitbit and Fitbit Ultra are reliable and valid for activity monitoring (step counts) and determining energy expenditure while walking and jogging without an incline. The Fitbit and standard accelerometers under-estimated energy expenditure compared to indirect calorimetry for inclined activities. These data suggest the Fitbit and Fitbit Ultra are reliable and valid for monitoring over-ground energy expenditure.     

Free-living physical activity and energy expenditure of rural children and adolescents in the Nandi region of Kenya

Abstract

Purpose: To examine the relationship between physical activity and energy demands in children and adolescents with highly active lifestyles.

Methods: Physical activity patterns of 30 rural Kenyan children and adolescents (14?±?1 years, mean?±?SD) with median body mass index (BMI) z-score?=??1.06 [?3.29–0.67] median [range] were assessed by accelerometry over 1 week. Daily energy expenditure (DEE), activity-induced energy expenditure (AEE) and physical activity level (PAL) were simultaneously determined using doubly-labelled water (DLW). Active commuting to school was assessed by global positioning system.

Results: Mean DEE, AEE and PAL were 12.2?±?3.4, 5.7?±?3.0?MJ/day and 2.3?±?0.6, respectively. A model combining body mass, average accelerometer counts per minute and time in light activities predicted 45% of the variance in DEE (p?<?0.05) with a standard error of DEE estimate of 2.7?MJ/day. Furthermore, AEE accounted for ～47% of DEE. Distance to school was not related to variation in DEE, AEE or PAL and there was no association between active commuting and adiposity.

Conclusion: High physical activity levels were associated with much higher levels of energy expenditure than observed in Western societies. These results oppose the concept of physical activity being stable and constrained in humans.     

Estimating energy expenditure using accelerometers

The purpose of this study was to examine the validity of published regression equations designed to predict energy expenditure (EE) from accelerometers (Actigraph, Actical, and AMP-331) compared to indirect calorimetry, over a wide range of activities. Forty-eight participants (age: 35 ± 11.4 years) performed various activities that ranged from sedentary behaviors (lying, sitting) to vigorous exercise. The activities were split into three routines of six activities, and each participant performed at least one routine. The participants wore three devices (Actigraph, Actical, and AMP-331) and simultaneously, EE was measured with a portable metabolic system. For the Actigraph, 15 previously published equations were used to estimate EE from the accelerometer counts. For the Actical, two published equations were used to estimate EE from the accelerometer counts. For the AMP-331 we used the manufacturer’s equation to estimate EE. The Actigraph and Actical regressions tended to overestimate walking and sedentary activities and underestimate most other activities. The AMP-331 gave a close estimate of EE during walking, but overestimated sedentary/light activities and underestimated all other activities. The only equation not significantly different from actual time spent in both light and moderate physical activity was the Actigraph Freedson kcal equation. All equations significantly underestimated time spent in vigorous physical activity (P < 0.05). In conclusion, no single regression equation works well across a wide range of activities for the prediction of EE or time spent in light, moderate, and vigorous physical activity.Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users.     

Increasing passive energy expenditure during clerical work

Sitting on a therapy ball or standing may be a passive means of increasing energy expenditure throughout the workday. The purpose of this study was to determine the energy expenditure and liking of performing clerical work in various postures. Subjects included 24 men and women employed in sedentary clerical occupations. Energy expenditure was measured while word processing in three standardized postures; sitting in an office chair, sitting on a therapy ball, and standing. Adults ranked their comfort, fatigue, and liking of each posture and were asked to perform their choice of 20 min of additional clerical work in one of the postures. Energy expenditure was 4.1 kcal/h greater (p ≤ 0.05) while performing clerical work while sitting on a therapy ball and standing than while sitting in an office chair. There was no difference in energy expenditure between the therapy ball and standing postures (p ≥ 0.48). Subjects also liked sitting on a therapy ball as much as sitting in an office chair and liked sitting on a therapy ball more than standing (p ≤ 0.05). More subjects chose to perform additional clerical work while seated on a therapy ball than while standing (p = 0.03). In conclusion, sitting on a therapy ball or standing rather than sitting in an office chair while performing clerical work increases passive energy expenditure.     

Metabolic efficiency and energy expenditure during short-term overfeeding

OBJECTIVE: To investigate whether efficiency of weight gain during a short period of overfeeding is related to adaptive differences in basal metabolic rate (BMR) and physical activity. SUBJECTS: Fourteen healthy females (age 25+/-4 years, BMI 22.1+/-2.3 kg/m2). DESIGN AND MEASUREMENTS: Subjects were overfed with a diet supplying 50% more energy than baseline energy requirements for 14 days. Overfeeding diets provided 7% of energy from protein, 40% from fat and 53% from carbohydrates. Body composition was determined using hydrodensitometry and isotope dilution, total energy expenditure (TEE) with doubly labeled water and basal metabolic rate (BMR) with indirect calorimetry. Physical activity (PA) was recorded with a tri-axial accelerometer. RESULTS: Body weight increased by 1.45+/-0.86 kg (mean+/-S.D.) (P<0.0001), fat mass increased by 1.05+/-0.75 kg. Energy storage was 57.0+/-17.9 MJ, which is the difference between energy intake (207.2 MJ) and energy expenditure (150.2 MJ) during overfeeding. There was no difference between metabolically efficient and metabolically inefficient subjects in changes in BMR and PA. CONCLUSION: These results indicate that the metabolic efficiency of weight gain was not related to adaptive changes in energy expenditure.     

Running promotes wakefulness and increases cataplexy in orexin knockout mice

STUDY OBJECTIVE: People with narcolepsy and mice lacking orexin/hypocretin have disrupted sleep/wake behavior and reduced physical activity. Our objective was to identify physiologic mechanisms through which orexin deficiency reduces locomotor activity. DESIGN: We examined spontaneous wheel running activity and its relationship to sleep/wake behavior in wild type (WT) and orexin knockout (KO) mice. Additionally, given that physical activity promotes alertness, we also studied whether orexin deficiency reduces the wake-promoting effects of exercise. MEASUREMENTS AND RESULTS: Orexin KO mice ran 42% less than WT mice. Their ability to run appeared normal as they initiated running as often as WT mice and ran at normal speeds. However, their running bouts were considerably shorter, and they often had cataplexy or quick transitions into sleep after running. Wheel running increased the total amount of wakefulness in WT and orexin KO mice similarly, however, KO mice continued to have moderately fragmented sleep/wake behavior. Wheel running also doubled the amount of cataplexy by increasing the probability of transitioning into cataplexy. CONCLUSIONS: Orexin KO mice run significantly less than normal, likely due to sleepiness, imminent cataplexy, or a reduced motivation to run. Orexin is not required for the wake-promoting effects of wheel running given that both WT and KO mice had similar increases in wakefulness with running wheels. In addition, the clear increase in cataplexy with wheel running suggests the possibility that positive emotions or reward can trigger murine cataplexy, similar to that seen in people and dogs with narcolepsy.     

Exercise-induced energy expenditure: Implications for exercise prescription and obesity

Objective

Walking is commonly recommended to help with weight management. We measured total energy expenditure (TEE) and its components to quantify the impact of increasing exercise-induced energy expenditure (ExEE) on other components of TEE.

Methods

Thirteen obese women underwent an 8-week walking group intervention. TEE was quantified using doubly labeled water, ExEE was quantified using heart rate monitors, daily movement was assessed by accelerometry and resting metabolic rate was measured using indirect calorimetry.

Results

Four of the 13 participants achieved the target of 1500 kcal wk⁻¹ of ExEE and all achieved 1000 kcal wk⁻¹. The average ExEE achieved by the group across the 8 weeks was 1434 ± 237 kcal wk⁻¹. Vigorous physical activity, as assessed by accelerometry, increased during the intervention by an average of 30 min per day. Non-exercise activity thermogenesis (NEAT) decreased, on average, by 175 kcal d⁻¹ (−22%) from baseline to the intervention and baseline fitness was correlated with change in NEAT.

Conclusions

Potential alterations in non-exercise activity should be considered when exercise is prescribed. The provision of appropriate education on how to self-monitor daily activity levels may improve intervention outcomes in groups who are new to exercise.

Practice implications

Strategies to sustain incidental and light physical activity should be offered to help empower individuals as they develop and maintain healthy and long-lasting lifestyle habits.     

Aggregation of physical activity habits in Mexican-American and Anglo families

It is believed that families are important influences on the development of health habits, and the purpose of the present study was to examine the familial aggregation of physical activity. Physical activity habits were assessed by standardized interview in adults and children in 95 Anglo families and 111 Mexican-American families. The results indicated a moderate degree of aggregation of physical activity in both samples, and adjustment for body mass index was inconsequential. Intrafamily correlations tended to be higher in Mexican-Americans. Mother-child correlations usually were higher than father-child correlations. These findings support the hypothesis that the family is a significant influence on physical activity.This work was supported by NIH Grant HL 30872 to Philip R. Nader, M.D.     

Comparisons in ambulatory physical activity in children from the United Kingdom and Belgium

Aim: This study sought to examine ambulatory physical activity levels in adolescents from the UK and Belgium.

Methods: Following ethics approval, 2760 children (1247 boys, 1513 girls), aged 9–14 years from Belgium (n?=?1614) and the UK (n?=?1146), wore a pedometer for 4 days including at least 1 weekend day. Body mass index (BMI) was determined from height and mass.

Results: A 2 (gender)?×?2 (country) way ANCOVA, controlling for age and BMI, revealed a significant country-by-gender interaction for steps/day (p?=?0.0001). In both Belgium and the UK, boys were more physically active than girls (both p?=?0.0001), but the difference between boys and girls was greater for Belgian than UK children.

Conclusion: These results suggest there are differences in the ambulatory physical activity patterns of children in the UK and Belgium.     

Prevalence of overweight,obesity and physical activity levels in children from Azores Islands

Abstract

Background: Childhood overweight and obesity are increasing all over the world and have been associated with low levels of physical activity (PA).

Aims: To determine the prevalence of overweight, obesity and PA levels in Azorean children according to age and sex; and to determine the association between levels of PA and prevalence of overweight and obesity.

Subjects and methods: Weight, height and PA levels were measured in 3699 children aged 6–10 years, from the Azores Islands, Portugal. Overweight and obesity were classified according to the cut-offs of .

Results: In girls, prevalences of overweight and obesity were 22.8% and 13.2%, and in boys 17.6% and 12.3%, respectively. No age trends were found in the prevalence of overweight or obesity; however, girls had a higher risk of being overweight (OR = 1.4, 95% CI = 1.2–1.7) than boys. Levels of PA were higher in boys compared to girls (F(1) = 52.8, p < 0.001). A protective effect of PA practice (very active versus less active) was observed for obesity (OR = 0.7; 95% CI = 0.5–0.9).

Conclusion: The results demonstrate the existence of high prevalence of overweight and obesity in children from the Azores Islands, which is associated with low levels of PA.     

Interaction between the genetic variant of rs696217-ghrelin and food intake and obesity and dyslipidemia

In this study, we aimed to investigate the relationship between the genetic variant of rs696217-ghrelin and fasted lipid profile, indices of obesity, and environmental parameters. Amplification refractory mutation system-polymerase chain reaction (ARMs-PCR) was used for genotyping 1118 individuals recruited as part of the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) cohort study. The interaction between the presence of the genetic variant of rs696217-ghrelin and nutritional intake and other major determinants of obesity and lipid profile was examined in the MASHAD study population. Individuals with the TT genotype at the locus had the lowest prevalence of obesity compared to other genotypes among the individuals. No significant relationship was found between the two groups regarding the lipid profile and TT genotype. Furthermore, no significant association was found between dietary intake and the genetic variant of rs696217-ghrelin in the population under study. Individuals with a TT or GT genotype appear to be at a higher risk of obesity, compared to those with a GG genotype. The results of the current study revealed a significant association between the genetic variant of rs696217-ghrelin and obesity; however, this gene did not correlate with the risk factors of cardiovascular diseases and dyslipidemia in the Iranian population.     

Effect of peers and friends on youth physical activity and motivation to be physically active

Objective To test whether the presence of a peer or a friendincreases the motivation to be physically active in overweightand non-overweight youth in a laboratory setting. Methods Youthmotivation to be physically active as a function of the socialcontext was measured using a computerized relative reinforcingvalue task to earn points exchangeable for physical and/or sedentaryactivities. Results The presence of a friend (p<.001)increased youth's; motivation to be physically active. The presenceof a peer increased overweight youth's; motivation to be physicallyactive, whereas this was not the case for lean youth (p=.47).Participants biked a greater distance in the presence of a friendthan when alone (p<.001). Overweight youth biked a greaterdistance in the presence of a peer than when alone, while thiswas not the case for lean youth (p=.23). Conclusions Friendshipsmay increase youth's; motivation to engage in physical activityand promote greater physical activity in non-overweight andoverweight youth.     

Physical activity and energy expenditure in lean and obese adult human subjects

Summary We compared the physical activity of 11 lean and 11 obese men and women over a 7-day period. There were no significant differences in either the amount of movement recorded with an accelerometer (9.5 (SD 3.9) vs 9.9 (SD 2.6) kcounts · day^–1), or in the energy expenditure due to physical activity reflected by the difference between the average daily metabolic rate measured by the doubly labelled water, technique and the sleeping metabolic rate measured in a respiration chamber and adjusted for fat-free mass: 112 (SD 33) vs 118 (SD 22) kJ · kg^–1·day^–1.The obese showed a non-significant loos of body of 0.5 (SD 1.1) kg, probably due to reduced intake during the 7-day intake recording period.