the prevalence rate of juvenile obesity 
 has broad and serious health implications , since obesity can increase the risks of type 2 
 diabetic mellitus ( t2 dm ) , hypertension , cardiovascular disease ( cvd ) , sleep apnea , and 
 cancer1 .
abnormal glucose tolerance , 
 disturbed glucose tolerance , and t2 dm have been identified as increasing the risk of 
 cognitive impairment , and are been known to induce cognitive damage , both of which are 
 early - stage symptoms of alzheimer s disease and dementia2 .
diabetes mellitus is also known to have adverse effects on the 
 peripheral nervous system leading to detrimental changes in brain structure and other 
 neurophysiological traits3 .
brain - derived neurotrophic factor ( bdnf ) is generated and distributed from platelets in the 
 peripheral and central nervous systems , endotheliocytes , smooth muscle , immunocytes , and 
 skeletal muscle .
it is a nerve growth and positively contributes to neurogenesis , 
 neurodegeneration , and hippocampal neural plasticity , and enhances memory and learning4 .
a lower than normal bdnf level has been 
 observed among individuals with obesity and t2dm5 , and this has been reported to bring about neuropsychosis , severe 
 depression , and alzheimer s disease6 , and 
 has also recently been found to affect metabolism in the skeletal muscles6 .
inflammatory factors are highly prevalent among individuals with obesity , t2 dm , and 
 metabolic syndrome , and such inflammatory factors are associated with obesity and 
 inactivity .
high levels of inflammatory factors have also been identified as an independent 
 factor in the progress of t2 dm and cvd7 .
research on regular exercise and related neurotrophic factors has determined that exercise 
 can be divided between that which greatly increases the resting bdnf level8,9,10 and that which does not11,12,13 , but the findings are not conclusive due 
 to variations in exercise mode and duration .
studied the effects of regular exercise on inflammatory factors by 
 observing middle - aged men and women over the course of 12 months during which they performed 
 60 minutes of exercise once a week .
there results show that as body mass index ( bmi ) 
 decreased with progression of the exercise training , serum il-6 and c - reactive protein ( crp ) 
 levels at rest decreased correspondingly .
christiansen et al.7 observed men and women over 12 weeks while they performed 6075 
 minutes of endurance training 3 times a week , accompanied by diet control .
they also 
 reported a decrease in resting levels of il-6 and monocyte chemoattractant protein-1 ( mcp-1 ) 
 after training .
in addition , crp levels increased after one intense bout of exercise15 , and a regular exercise training group had 
 lower levels of crp than a control group16 .
although , the relationship between neurotrophic and inflammatory factors and regular 
 exercise has been investigated in recent research , the debate on whether regular exercise 
 can alter the resting bdnf level and inflammatory factor levels continues , and existing 
 research on the subject mainly concerns adults and the elderly .
insufficient research has 
 been conducted on juvenile obesity and t2 dm , which are rapidly increasing .
as adolescence 
 marks an important period of learning and development , the investigation of the effects of 
 regular exercise on juvenile obesity and t2 dm is indispensable . in this study
, we examined the effects of exercise by measuring the resting levels of 
 neurotrophic factors ( bdnf , ngf , and tropomyosin receptor kinase b [ trkb ] ) , and inflammatory 
 factors ( il-6 , tumor necrosis factor  [ tnf- ] , and crp ) of juveniles assigned to an obesity 
 group ( og , n = 8) , t2 dm group ( tg , n = 7 ) , and control group ( cg , n = 11 ) following 12 weeks 
 of aerobic exercise 3 times a week .
we hypothesized that juveniles with obesity and t2 dm would have lower resting bdnf levels , 
 and that 12 weeks of regular exercise would result in increased levels of resting 
 neurotrophic factors and decreased levels of inflammatory factors .
this experiment initially recruited originally began with 45 teenagers who were assigned to 
 the og ( n = 15 ) , tg ( n = 15 ) , and cg ( n = 15 ) .
however , due to withdrawals , only 26 
 teenagers in the og ( n = 8 , boys = 4 , girls = 4 , age ; 16.3 0.91 ) , tg ( n = 7 , boys = 2 , 
 girls = 5 , age ; 15.5 2.14 ) , and cg ( n = 11 , boys = 11 , age ; 16.4 1.36 ) completed the 12 
 weeks program .
all participants were between the ages of 13 and 19  years , and there were 17 
 boys and 9 girls .
the og teenagers were selected based on the 1998 standards for children 
 and juvenile growth of the korean pediatrics society : bmi > 95th percentile , or obesity 
 index > 120% .
the tg teenagers were selected from among d university hospital out - patients 
 whose 2-hour glucose tolerance test was 140  mg / dl  blood sugar  200  mg / dl , and who had no 
 other complicating diseases .
the cg was created by age - matching with the tg and og 
 juveniles .
the 
 study was approved by the d university hospital institutional review board ( irb ) and the 
 subjects were included after medical examination and diagnosis by medical specialists
. 
 additionally , signed consent forms were obtained from the guardians of all participants 
 prior to the commencement of the study .
height , weight , and bmi were measured as the physical characteristics , and body fat 
 percentage was measured using an impedance analyzer ( venus 5.5 , jawon medical , gyeongsan , 
 korea ) .
changes in baseline characteristics following 12 weeks of aerobic exercise 
 trainingvariablegroupbaseline12 weeksage(yrs)cg16.451.36og16.370.91tg15.572.14height(cm)cg171.115.17171.34*5.07og171.226.31172.255.93tg161.157.70161.277.86weight(kg)cg65.9214.5866.1014.84og80.207.5073.06*10.91tg61.8413.6862.6114.23bmi(kg / m)cg22.353.9422.374.07og27.472.5124.70*3.24tg23.724.4724.074.52body fat(%)cg16.566.9616.847.18og31.775.1925.52*5.52tg28.204.7727.187.73vo2max(ml kg 
 min)cg33.283.7633.973.44og29.205.4533.91*4.60tg28.604.8832.86*4.56means sd .
cg , control group ; og , obesity group ; tg , t2 dm group .
a , significant difference 
 ( p<0.05 ) cg vs. og ; b , significant difference og vs. tg ; c , significant difference 
 cg vs. tg .
a submaximal oxygen consumption exercise test ( 85% vo2submax test ) 
 was conducted before the start of the exercise training .
all participants were tested on a 
 quinton q65 treadmill ( quinton co. , usa ) in a laboratory with 5055% humidity and a 
 temperature 2425  c .
the subjects wore a polar system ( polar electro , kempele , finland ) , 
 and were measured using a breath - by - breath test .
each respiration was automatically measured 
 for ventilatory volume , oxygen consumption , carbon dioxide emission , respiratory exchange 
 ratio ( rer ) , and heart rate ( hr ) .
cg , control group ; og , obesity group ; tg , t2 dm group .
a , significant difference 
 ( p<0.05 ) cg vs. og ; b , significant difference og vs. tg ; c , significant difference 
 cg vs. tg the exercise test was conducted using a treadmill exercise test and the bruce protocol17 .
this method involves steadily increasing 
 the exercise level until the target heart rate ( thr ) reaches 85% of the maximum oxygen 
 consumption ( vo2max ) .
no subjects exhibited cardiac abnormalities or high blood 
 pressure before reaching the thr . to prevent accidents ,
participants were asked to 
 subjectively identify the intensity of exercise on the borg scale of rate of perceived 
 exertion18 .
aerobic exercise was conducted for a total of 4060 minutes per session , 3 sessions a week , 
 for 12 weeks .
participants attained 50% of their oxygen consumption as measured by the 
 vo2max test . between week 1 and week 4 , they engaged in 3040 minutes 
 walking / running aerobic exercise on a school field under the instruction of a professional 
 trainer while wearing a polar system at a calculated heart rate recovery ( hrr ) of 50% 
 vo2max . between week 5 and week 12 , the participants exercised in a similar 
 manner but for 4050 minutes at a hrr equivalent to 60% of vo2max .
each session 
 was preceded and followed by a 5-minute warm up and cool down , respectively .
samples were 
 centrifuged at 3,000  rpm for 10 minutes , stored at 80  c , and directly analyzed .
the biochemical analyses of serum il-6 , tnf- , and ngf were performed using enzyme - linked 
 immunosorbent assays for quantitative detection of human il-6 , tnf- ( ebioscience , vienna , 
 austria ) and ngf ( abcam , ma , usa ) .
all factors were quantified using polyclonal antibodies 
 that recognized native human il-6 , tnf- , or ngf and a series of plates containing wells 
 coated with predetermined amounts of recombinant human il-6 , tnf- , or ngf .
serum bdnf levels were analyzed with an r & d system ( minneapolis , minn .
, usa ) kit and 
 serum trkb levels were analyzed with a sino biological kit ( sino biological inc , beijing , 
 china ) .
then , substrate solution and 
 streptavidin - hrp were added , the reaction was terminated with a stop solution , and the 
 results obtained by measuring the optical density at 450  nm .
serum crp was analyzed with an automatic analyzer ( adipogen , seoul , korea ) using latex 
 cohesion turbidimetry with a crp(ii ) x2 latex reagent .
for all data , the mean and standard deviation were calculated using spss for windows ver . 

repeated measures two - way anova was used to control for 
 differences between groups , test periods , physical characteristics , and biochemical blood 
 component changes caused by exercise , using scheffe s method for the post hoc test . 

subjects physical characteristics were recorded at baseline and after the 12 weeks of 
 regular aerobic exercise .
there were no significant differences in weight among the groups , but 
 there was a difference between the test periods .
there was an interaction effect between 
 group and time ( f = 12.779 , p<0.05 ) , and further analysis of the interaction effect 
 revealed a significant weight reduction ( p<0.05 ) in the og after the 12 weeks of regular 
 exercise .
there were no significant differences in bmi among the groups , but there was a significant 
 difference between the test periods ( f = 8.011 , p<0.05 ) .
there was an interaction effect 
 between group and time ( f = 12.685 , p<0.05 ) , and further analysis of the interaction 
 effect revealed a significant bmi reduction ( p<0.05 ) in the og after the 12 weeks of 
 regular exercise .
there were significant differences in body fat percentage among the groups ( f = 10.726 , 
 p<0.05 ) and test periods ( f = 16.820 , p<0.05 ) .
there was an interaction effect between 
 group and time ( f = 12.898 , p<0.05 ) , and further analysis of the interaction effect 
 revealed a significant body fat percentage reduction ( p<0.05 ) in the og after the 12 
 weeks of regular exercise .
there were no significant differences in the vo2max among groups , but the 
 vo2max between the test periods differed significantly ( f = 19.348 , p<0.05 ) . 

there was an interaction effect between group and time ( f = 3.441 , p<0.05 ) , and further 
 analysis revealed a significant vo2max increase ( p<0.05 ) in the og and tg 
 after the 12 weeks of regular exercise .
the serum bdnf , ngf , and trkb levels were recorded at baseline and after the 12 weeks of 
 regular aerobic exercise .
changes of the serum neurotrophic factors and inflammatory factors following 12 
 weeks of aerobic exercise training.variablegroupbaseline12-weekbdnf(pg/ml)cg21,178.33 4,306.1420,670.405,021.47og8,003.796,559.1019,617.53*8,098.60tg25,136.143,814.1625,104.585,389.95ngf(pg / ml)cg5.142.356.211.78og8.838.6630.5544.04tg5.583.337.808.86trkb(pg / ml)cg182.7132.07187.1165.44og123.2050.80146.7729.98tg112.0240.30143.8556.52il-6(pg / ml)cg1.422.851.472.84og0.900.421.521.42tg0.920.720.610.40tnf-(pg / ml)cg3.351.748.1213.33og4.271.733.711.89tg3.181.772.930.84crp(mg / dl)cg0.100.060.220.45og0.150.130.130.19tg0.060.050.080.09means sd .
cg , control group ; og , obesity group ; tg , t2 dm group .
a , significant difference 
 ( p<0.05 ) cg vs. og ; b , significant difference og vs. tg ; c , significant difference 
 cg vs. tg .
there was a significant difference in bdnf levels among the groups ( f = 
 13.673 , p<0.05 ) and test periods ( f = 6.338 , p<0.05 ) .
there was an interaction effect 
 between group and test period , and further analysis of the interaction effect revealed a 
 significant bdnf increase ( p<0.05 ) in the og after the 12 weeks of regular exercise .
cg , control group ; og , obesity group ; tg , t2 dm group .
a , significant difference 
 ( p<0.05 ) cg vs. og ; b , significant difference og vs. tg ; c , significant difference 
 cg vs. tg there were no significant difference in ngf levels among the groups or test periods , and 
 there was no interaction effect between group and test period .
there was a significant difference in trkb levels among the groups ( f = 6.400 , p<0.05 ) , 
 but there was no interaction effect between group and test period .
the 12 weeks regular aerobic exercise resulted in little changes in the inflammatory 
 factors ( serum il-6 , tnf- , crp ) .
there were no significant differences or interaction 
 effects of il-6 , tnf- , and crp among groups , or between test periods , or group and test 
 period .
we aimed to test whether 12 weeks of regular aerobic exercise would have a positive effect 
 on neurotrophic and inflammatory factors .
as described earlier , bdnf is mainly responsible for nerve survival , growth , maintenance , 
 learning , and memory .
patients with alzheimer s disease exhibit low levels of bdnf 
 expression in the hippocampus19 and low 
 serum bdnf20 .
similarly , patients with 
 parkinson s disease and huntington s disease have low levels of hippocampal bdnf21 , and patients with depression have low 
 levels of serum bdnf22 .
this experiment 
 revealed that the resting bdnf level at baseline before the 12 weeks of aerobic exercise was 
 significantly lower ( p<0.05 ) in the og than in the cg .
this result is in agreement with 
 previous research5 , which has reported low 
 levels of bdnf among people with obesity and t2 dm .
it also agrees with the findings of 
 previous research conducted on adults , which revealed that bdnf plays a very important role 
 in controlling energy homeostasis and weight23 , 24 , and has an inverse relation with weight 
 and age25 .
it is also was interesting to note that the tg and cg had similar resting bdnf levels , 
 i.e. , the resting bdnf levels of the tg teenagers of normal weight were not greatly 
 depressed .
this raises the question as to whether the resting bdnf levels of juveniles with 
 t2 dm have a greater effect on body composition , such as weight , than the disease itself .
another interesting point is that after 12 weeks of regular aerobic exercise , the resting 
 bdnf level of the og increased to 19,617  pg / ml , a level close to the adult normal range of 
 22,600  pg / ml25 .
this was a significant 
 increase ( p<0.05 ) and it was only observed in the og ( table 2 ) .
we suggest that there was no significant increase in the 
 resting bdnf level after the 12 weeks of exercise in the tg , because the exercise did not 
 result in significant changes in body composition ( weight , bmi , body fat percentage ) .
trkb is a bdnf receptor that is expressed abundantly and widely in the brain26 , and ngf plays an important role in the 
 sustenance of sympathetic and sensory neurons as well as biological activities , including 
 cell growth27 .
schulz et al.13 studied the effects of 8 weeks of aerobic 
 ergometry exercise on patients with multiple sclerosis ( ms ) , and reported no significant 
 difference in the ngf level of the exercise group .
bansi et al.28 conducted 3 weeks of regular exercise ( aquatic vs. 
 overland ) for middle - aged patients with multiple sclerosis and also failed to significantly 
 alter resting ngf levels . while our present findings did not reveal a significant difference 
 in resting ngf levels in the og , compared to the cg and tg
a 
 previous study of 146 adults29 , also 
 reported the ngf levels of obese subjects were higher than those of normal weight subjects . 

although trkb levels increased in the og and tg following the 12 weeks of aerobic exercise , 
 there was no significant difference between the two groups .
however , comparison of the 
 resting trkb levels of the cg with og and tg at baseline revealed that og and tg had 
 significantly lower resting trkb levels than cg , and we consider this proof of them having 
 decreased bdnf receptor levels , as trkb is a bdnf receptor ( table 2 ) .
one of the limitations of this experiment was that while there have been many studies of 
 neurotrophic factor bdnf , few human studies of ngf and trkb have been conducted .
this 
 renders comparative analysis difficult , and much more research concerning ngf and trkb 
 levels will need to be conducted in the future .
high levels of inflammatory cytokines are observed in patients with obesity , t2 dm , and ms , 
 and such high levels of inflammatory factors are an independent factor in the development of 
 cvd7 .
additionally , arteriosclerosis and 
 coronary artery disease are associated with increased levels of il-6 , crp , and tnf-30 , 31 , and higher il-6 and crp have been observed in metabolic disabilities 
 such as t2 dm , ms , and obesity31 , 32 .
il-6 , a typical inflammatory factor , is a multifunctional cytokine responsible for 
 pleiotropism in immunomodulation33 , and 
 was recently reported to be a myokine , involved in energy metabolism in skeletal muscle34 .
crp also serves as an indicator of 
 systemic inflammatory response . an increased crp level in obese patients
is explained by 
 il-6 originating from adipose tissue , and crp levels are significantly decreased by aerobic 
 exercise and diet35 .
christiansen et 
 al.7 conducted a study of men and women 
 engaged in aerobic exercise lasting 6075 minutes per session , 3 sessions a week for 12 
 weeks .
they noted that there were no significant reductions in il-6 , il-15 , il-18 , or mcp-1 
 without dieting or significant reductions in weight .
kohut et al.36 studied patients with metabolic disease who showed no 
 reduction in weight over the course of 10 months by comparing a group that did aerobic 
 exercise for 45 minutes per session , 3 sessions a week , with a resistance / flexibility 
 training group .
they found that the aerobic exercise group showed significant reductions in 
 crp , l-6 , and il-18 .
additionally , a study of middle - aged men and women performing endurance 
 exercise , consisting of one 60-minute training session per week for 12 months , reported a 
 significant decrease in serum crp levels following a reduction in bmi14 .
to date , reducing circulating inflammatory factors has been proposed to be associated with 
 weight reduction37 and adipose tissue 
 reduction36 , 38 , 39 , but our 12 weeks of 
 exercise failed to result in a significant reduction in inflammatory factors ( especially 
 il-6 ) in the og , despite a significant reduction in weight , body fat percentage , and bmi .
we 
 believe that , compared to the 1012-month study periods of other experiments14 , 36 
 that saw reductions in il-6 through regular training , the exercise period of this study was 
 too short to reduce resting il-6 levels .
another interesting point is that this study 
 recorded very low levels of il-6 ( 0.91.4  pg / ml ) compared to the average resting il-6 level 
 ( 3.45.0  pg / ml ) reported by previous studies of adults ( healthy people in their 30s and 
 middle - aged patients with t2 dm ) and the elderly over 64  years of age7 , 14 , 36 , 40 . as the immune 
 and inflammatory systems progressively change with age41 ,
perhaps the subjects youth may have been a factor influencing 
 their lower il-6 levels , despite their obesity and t2 dm .
the resting il-6 levels of the 
 teenagers were also close to the 1.11.6  pg / ml of young adults aged between 20 and 30  years 
 with simple obesity42 .
previous research related to exercise has reported significant reductions in inflammatory 
 factors ( il-6 , tnf- , hs - crp ) following long - term training lasting 1012 months14 , 36 
 rather than a 12-week period42 , 43 .
the only exception was an 8-week aerobic training and 
 diet restriction study of a group of children with obesity .
that study reported a 
 significant reduction in inflammatory markers ( il-6 , tnf- , hs - crp ) , and it argued that the 
 significant changes in body composition ( body weight , bmi , body fat percentage ) , induced by 
 exercise and diet restriction , had a strong effect on the inflammatory factors44 .
we also observed slight changes in tnf- and crp levels after the 12 weeks of aerobic 
 exercise , but did not find significant differences , in agreement with previous studies40 , 42 , 43 .
taken together , our present results and 
 those of other studies40 , 45 indicate that exercise has limited or no effect on 
 inflammatory markers .
while many studies of exercise effects have been conducted using adults and the elderly , 
 comparisons with our results were limited by the lack of researches involving juveniles 
 between the ages of 13 and 17  years , and differences in training period , exercise intensity , 
 exercise frequency , and sample size used in the other studies of bdnf and inflammatory 
 markers . the juveniles with obesity and
t2 dm exhibited reduced levels of resting neurotrophic 
 factors ( bdnf , trkb ) at baseline , but after the 12 weeks aerobic exercise , there was a 
 significant increase in the bdnf level of the og .
however , these findings are limited , and 
 the effects of regular exercise on neurotrophic factors and inflammatory factors in juvenile 
 obesity and t2 dm were not conclusively proven .
   [ purpose ] the purpose of this study was to investigate the effects of 12 weeks regular 
 aerobic exercise on brain - derived neurotrophic factor ( bdnf ) and inflammatory factors in 
 juvenile obesity and type 2 diabetes mellitus ( t2 dm ) . 
 obesity and t2 dm , typically common 
 among adults , have recently become more prevalent in the korean juvenile population , 
 affecting not only their lipid profiles and oxidant stress levels , but also their bdnf and 
 inflammatory factor levels . 
 [ subjects ] this study enrolled 26 juveniles ( boys = 15 , girls 
 = 9 ) who were assigned to a control group ( cg , n = 11 ) , obesity group ( og , n = 8) , or t2 dm 
 group ( tg , n = 7 ) . 
 [ methods ] the outcome of a 4060-minute aerobic exercise session that 
 took place three times per week for 12 weeks at a maximum oxygen intake 
 ( vo2max ) of 50~60% was investigated . 
 [ results ] the exercise resulted in a 
 significant reduction in the resting serum bdnf and trkb levels ( baseline ) among juveniles 
 in the og and tg as compared to those in the cg . 
 additionally , the 12 weeks of regular 
 aerobic exercise led to significant reductions in body weight , body fat percentage , and 
 body mass index in the og and a significant increase of vo2max in the og and 
 tg . however , no significant differences in serum ngf or inflammatory factors were found 
 among the three groups . there was a significant increase in resting serum bdnf levels 
 following the 12 weeks regular exercise only in the og . 
 [ conclusion ] while 12 weeks of 
 regular aerobic exercise had a positive effect on body composition , and increased bdnf 
 levels of juveniles in the og , it did not affect the inflammatory factor levels and had no 
 effect on the tg . 
INTRODUCTION
SUBJECTS AND METHODS
RESULTS
DISCUSSION