***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background Cold-stimulated adaptive thermogenesis in brown adipose tissue ( BAT ) to increase energy expenditure is suggested as a possible therapeutic target for the treatment of obesity . We have recently shown high prevalence of BAT in adult humans , which was inversely related to body mass index ( BMI ) and body fat percentage ( BF% ) , suggesting that obesity is associated with lower BAT activity . Here , we examined BAT activity in morbidly obese subjects and its role in cold-induced thermogenesis ( CIT ) after applying a personalized cooling protocol . We hypothesize that morbidly obese subjects show reduced BAT activity upon cold exposure . Methods and Findings After applying a personalized cooling protocol for maximal non-shivering conditions , BAT activity was determined using positron-emission tomography and computed tomography ( PET-CT ) .  Cold-induced BAT activity  was detected in three out of 15 morbidly obese subjects . Combined with results from lean to morbidly obese subjects ( n = 39 ) from previous study , the collective data show a highly significant correlation between BAT activity and body composition ( P<0.001 ) , respectively explaining 64 % and 60 % of the variance in BMI ( r = 0.8 ; P<0.001 ) and BF% ( r = 0.75 ; P<0.001 ) . Obese individuals demonstrate a blunted CIT combined with low BAT activity . Only in BAT-positive subjects ( n = 26 ) mean energy expenditure was increased significantly upon cold exposure ( 51.5±6.7 J/s versus 44.0±5.1 J/s , P = 0.001 ) , and the increase was significantly higher compared to BAT-negative subjects ( + 15.5±8.9 % versus + 3.6±8.9 % , P = 0.001 ) , indicating a role for BAT in CIT in humans . Conclusions This study shows that in an extremely large range of body compositions , BAT activity is highly correlated with BMI and BF% . BAT-positive subjects showed higher CIT , indicating that BAT is also in humans involved in adaptive thermogenesis . Increasing BAT activity could be a therapeutic target in ( morbid ) obesity The cage systems commonly used for housing laboratory rats often result in sedentary and overweight animals , as a consequence of restricted opportunities for physical activity combined with ad libitum feeding . This can have implication s both for animal well-being and for the experimental outcome . Physical activity has several known positive effects on health and lifespan , and physical fitness might therefore be incorporated into the animal welfare concept . The aim of this study was to investigate if and how pen housing affects the physical activity and fitness of rats . Thirty-two juvenile male Sprague-Dawley rats were r and omly assigned to two different housing systems for a 4-week period . Sixteen rats were kept individually in st and ard Makrolon type III cages ( 42 × 26 × 18 cm ) furnished with black plastic tubes ( singly-housed , SI ) . The remaining rats were kept in groups of eight , housed in large floor pens ( 150 × 210 cm ) , which were furnished with various objects to increase environmental complexity ( pen-housed , PH ) . The body weight gain , and food and water intake of the rats were measured . During weeks 3 or 4 , home cage behaviour , urinary cortiosterone/creatinine ratios ( CO/CR ) , and muscle strength on an inclined plane , were measured . Enzyme activities and glycogen content were measured in tissue sample s from m. triceps brachii taken after euthanization at the end of the study . There were no significant differences between groups for food and water intake , but PH rats weighed 14 % less than SI rats after 4 weeks , and PH rats also had a more diverse behavioural pattern than SI rats . PH rats had significantly higher oxidative capacity ( 28 % more citrate synthase ( CS ) ) and greater glycogen content ( 28 % ) in their muscle sample s than SI rats . The PH rats performed significantly better on the inclined plane , both in the muscle strength test ( mean angle 75 ± 0.5 ° for PH rats and 69 ± 0.4 ° for SI rats ) and the endurance strength test ( mean time 233 ± 22 s for PH rats and 73 ± 14 s for SI rats ) . There was a negative correlation between body weight and results on the inclined plane for the PH rats . There were no significant differences between housing types with respect to CO/CR ratios . In conclusion , the large pen represents an environment that stimulates physical activity and more varied behaviour , which should be beneficial for the welfare of the animal Currently , environmental enrichment is a very common means of improving animal well-being , especially for laboratory animals . Although environmental enrichment seems to be a possible way for improving the well-being of animals , the consideration of housing laboratory animals should not only focus solely on animal well-being , manpower and economics but also on the precision and accuracy of the experimental results . The purpose of the present study was to evaluate the effects of enriched cages ( nest box , nesting material , climbing bar ) on body weight , haematological data and final organ weights .  BALB/c , C57BL/6 and A/J mice , originated from Harlan Winkelmann , were used for the experiments - 16 animals of each strain . Animals at 3 weeks of age were marked and separated r and omly to enriched or non-enriched cages , in groups of four , half for each housing condition . Both cages were type III Makrolon cages , only the enriched cages contained a nest box , a wood bar for climbing and nesting material . Animals were kept in a clean animal room under specific pathogen free ( SPF ) conditions . Body weights were recorded every week . Blood sample s were collected at 14 weeks of age ( white blood cells ( WBC ) , red blood cells ( RBC ) , haemoglobin ( HGB ) , and haematocrit ( HCT ) were analysed ) . At 15 weeks of age , the animals were euthanized by CO2 in their home cages , and final body weight and organ weights ( heart , liver , kidney , adrenal , spleen and uterus ) were recorded immediately . Although nearly all the test variables were not affected by environmental enrichment in their mean values , the enriched group showed higher coefficients of variation in many variables , and strain differences of both housing conditions were not consistent . The influences of enrichment were shown to be strain- and test-dependent . Such effects may lead to an increase in the number of animals which is necessary or may change the experimental results , especially when a study , using enriched housing conditions , focuses on strain differences . Since the same enrichment design can result in different influences , a positive or a negative or no adverse effect , due to the strain and the variables studied , research ers need to collect more information before enrichment design s are introduced into experimental plans Ad libitum fed male Sprague-Dawley rats were r and omly assigned to be housed individually ( n=32 ) or four in each cage ( n=32 ) from five to 23 months of age .  Body weight and body composition by bioimpedance analysis were monitored longitudinally . An equation for analysis of body composition was developed . Deaths and causes of death were recorded . Of the individually housed animals ( H1 ) 16 percent died , while 44 percent of those housed four in a cage ( H4 ) died , the most common causes of death being circulatory failure , nephritis and tumours of the hypophysis . Body weight increased in both groups over time , significantly more for H4 from 6months of age . Both fat free mass and total body fat increased in both groups over time . Fat in percent of body weight increased up to an age of 14months . H4 animals had significantly more fat from 11 to 20 months of age but lost weight , mostly fat when approaching 23months of age . The occiput-sacrum length of the animals increased up to 11months of age and stayed then constant . Animals in both groups grew also in the cross-sectional dimension . The H1 animals continued to grow all the time , while the growth of the H4 animals stopped at the age of 17 months , when the mortality started to become pronounced . It is concluded that housing conditions can modulate the outcome of the ageing of sedentary and otherwise not treated rats in long-term experiments . Further , the feasibility of monitoring body composition longitudinally with bioimpedance analysis was demonstrated The aim of the present study was to investigate the effects of glucocorticoids ( GCs ) on appetite and gene expression of the hypothalamic appetite regulatory peptides , neuropeptide Y ( NPY ) , agouti-related protein ( AGRP ) and cocaine and amphetamine-regulated transcript ( CART ) , in non-obese and obese rats . Both non-obese and obese rats were r and omly assigned to three groups : normal saline , low- and high-dose GC groups ( NSG , LDG and HDG , respectively ) , which received an intraperitoneal injection with normal saline ( 0.2 ml/100 g ) or hydrocortisone sodium succinate at 5 and 15 mg/kg , respectively , for 20 days . The expression levels of NPY , AGRP and CART mRNA in the hypothalamus were measured by real-time quantitative PCR . Non-obese and obese rats were found to undergo weight loss after GC injection , and a higher degree of weight loss was observed in the HDG rats . The average and cumulative food intakes in the obese and non-obese rats injected with high-dose GC were lower compared to that in the NSG ( p<0.05 ) . mRNA expression levels of the orexigenic neuropeptides , NPY and AGRP , and the anorexigenic neuropeptide , CART , were significantly lower in the HDG than levels in the NSG for both the obese and non-obese rats ( p<0.05 ) . GC treatment decreased appetite and body weight , induced apparent glucolipid metabolic disturbances and hyperinsulinemia , while down-regulated mRNA expression levels of the orexigenic neuropeptides , NPY and AGRP , and anorexigenic neuropeptide , CART , in the hypothalamus in the rats . The mechanism which induces this neuropeptide expression requires further study Background Systematic Review s ( SRs ) of experimental animal studies are not yet common practice , but awareness of the merits of conducting such SRs is steadily increasing . As animal intervention studies differ from r and omized clinical trials ( RCT ) in many aspects , the methodology for SRs of clinical trials needs to be adapted and optimized for animal intervention studies . The Cochrane Collaboration developed a Risk of Bias ( RoB ) tool to establish consistency and avoid discrepancies in assessing the method ological quality of RCTs . A similar initiative is warranted in the field of animal experimentation . Methods We provide an RoB tool for animal intervention studies ( SYRCLE ’s RoB tool ) . This tool is based on the Cochrane RoB tool and has been adjusted for aspects of bias that play a specific role in animal intervention studies . To enhance transparency and applicability , we formulated signalling questions to facilitate judgment . Results The result ing RoB tool  for animal studies contains 10 entries . These entries are related to selection bias , performance bias , detection bias , attrition bias , reporting bias and other biases . Half these items are in agreement with the items in the Cochrane RoB tool . Most of the variations between the two tools are due to differences in design between RCTs and animal studies . Shortcomings in , or unfamiliarity with , specific aspects of experimental design of animal studies compared to clinical studies also play a role . Conclusions SYRCLE ’s RoB tool is an adapted version of the Cochrane RoB tool . Widespread adoption and implementation of this tool will facilitate and improve critical appraisal of evidence from animal studies . This may subsequently enhance the efficiency of translating animal research into clinical practice and increase awareness of the necessity of improving the method ological quality of animal studies 
    Output:
    
Whilst housing did not affect body weight , both food intake and visceral adipose tissue mass were significantly higher in individually compared with socially housed animals .
A combination of emotional stress and lack of social thermoregulation likely contributed to these effects .