total daily energy expenditure consists of three factors : resting metabolic rate ( rmr ) , 
 thermic effect of food intake ( tef ) , and physical activity1 . in general
, rmr is the most important component accounting for 
 6075% of total daily energy expenditure .
tef is defined as the increase in energy 
 expenditure in response to food intake and it accounts for 10% of total daily energy 
 expenditure1 .
it has been accepted that 
 sympathetic nervous system activity ( sna ) plays a role in regulation of energy expenditure 
 after food intake , because the thermic response is reduced by -adrenergic blockade2 , 3 . 

previous studies have shown that food intake increases energy expenditure , and is 
 accompanied by an increase in whole body sna ( for example , skeletal muscle , abdominal 
 tissue , adrenal medulla , and kidneys)2 , 4 , 5 .
preganglionic fibers of the sympathetic nervous system exit from the spinal cord between t1 
 and l2 and synapse with their respective ganglion , at which postganglionic neurons originate 
 and eventually project to their target organs6 .
the sympathetic nerves originating from t1 to t6 mainly innervate 
 the organs of the head and upper thorax , such as the lungs and heart , while the sympathetic 
 nerves originating below t7 mainly innervate the organs in the lower thorax , such as the 
 kidneys and adrenal glands .
furthermore , the sympathetic nerves innervating the adrenal 
 medulla originate between the t5 and t9 segments7 .
because supraspinal control of sympathetic preganglionic neurons is 
 interrupted in persons with cervical and higher thoracic spinal cord injury ( sci ) , sci often 
 results in autonomic dysfunction as well as motor and sensory deficits in the upper and/or 
 lower extremities .
several studies have reported that sna is decreased in subjects with 
 cervical and higher thoracic cord injury as compared to able bodied subjects ( ab)8,9,10,11 , 
 and this decrease in sna may blunt tef , as reported in elderly persons12 .
it is evident that subjects with sci have a higher fat mass and a 
 lower lean muscle mass than ab subjects , even though they have a normal body mass index 
 ( bmi ) value16 .
therefore , sci patients 
 may have a lower tef due to reduction in lean muscle mass as well as autonomic dysfunction , 
 which would increase their risk of developing obesity , and obesity - related disorders , such 
 as type 2 diabetes , cardiovascular diseases , and dyslipidemia .
however , little is known 
 about tef in subjects with higher thoracic sci ( hsci ) and lower thoracic sci ( lsci ) .
if sna 
 plays an important role in the regulation of tef , subjects with hsci would exhibit a greater 
 decrease in tef than lsci and ab subjects . to test this hypothesis
, we examined the time 
 courses of the tef among the three groups of subjects ( ab , hsci , and lsci ) and assessed the 
 relative contribution of the level of spinal cord injury to the tef .
seven male subjects with sci and six ab subjects ( controls ) , who were age- and 
 gender - matched , participated in this study .
all the scis were of traumatic origin and the 
 level of injury in the subjects with sci was between t5 and t12 ( table 1table 1.group averages of physiological characteristicsab ( n=6)hsci ( n=3)lsci ( n=4)age ( years)37.2  7.640.0  8.539.8  4.9weight ( kg)75.7  9.662.7  11.665.5  7.3height ( cm)173.7  7.3173.0  6.1174.8  5.1bmi ( kg / m)25.0  2.321.0  4.321.5
ab : able - bodied subjects ; sci : spinal cord injury ; hsci : higher thoracic sci 
 subjects ; lsci : lower thoracic sci subjects ) .
all the persons with paraplegia were examined clinically and 
 neurologically to classify the extent of spinal cord injury according to the american 
 spinal injury association ( asia ) impairment scale grade ( ais ) .
six individuals were 
 classified with a complete injury ( ais a ) , and one with an incomplete injury ( ais b ) . 

neurological examinations were performed by an approved physical therapist working in the 
 rehabilitation hospital .
the experimental procedures of this study were approved by the ethical 
 committee of the graduate school of integrated arts and sciences , hiroshima university , 
 and the study was performed in accordance with the ethical principles of the declaration 
 of helsinki .
all the subjects gave their written , informed consent before participating in 
 the present study .
ab : able - bodied subjects ; sci : spinal cord injury ; hsci : higher thoracic sci 
 subjects ; lsci : lower thoracic sci subjects all experiments were performed between 8:30 a.m. and 12:30 p.m. after an overnight fast 
 of 12 hours .
subjects were instructed not to exercise and to refrain from alcohol , 
 caffeine , and smoking for 24 hours preceding the experiments .
they were asked to refrain from taking 
 their medication on the day to minimize possible confounding effects on energy 
 expenditure .
all the subjects were also instructed to empty their bladders prior to the 
 experiments .
bmi was calculated as body weight ( kg ) divided by height squared 
 ( m ) .
each subject sat on their own wheelchair or a prepared chair during the 
 experiment in thermoneutral environment ( temperature , 2327  c ; relative humidity , 
 approximately 60% ) .
after 15  min of quiet rest , expiration gas was analyzed with a gas 
 analyzer ( ae-300s minato medical science co. , ltd , japan ) to measure oxygen consumption 
 ( vo2 ) and carbon dioxide production ( vco2 ) . at the end of the 
 resting period ,
a venous blood sample was taken from an antecubital vein to measure plasma 
 catecholamine concentrations .
plasma catecholamine concentrations were analyzed by a hplc method 
 ( fukuyama medical laboratory co. , ltd , japan ) .
heart rate ( hr ) was measured continuously 
 both at rest and during the postprandial period with a heart rate monitor ( polar s610i , 
 japan ) .
energy expenditure was calculated from vo2 and vco2 using the 
 formulas outlined by frayn17 .
the tef 
 was calculated as the area under the curve above the baseline level for 3 hours after food 
 intake and expressed as the absolute and adjusted values against body weight .
the test meal , which was consumed within 10  min by the subjects , consisted of portions of 
 calorie mate block and one calorie mate can ( otsuka pharmaceutical co. , ltd , japan ) .
the 
 test meal size and the number of blocks were determined using subjects body weights , to 
 achieve the same consumption of 7.9  kcal / kg of body weight18 .
therefore , total caloric content consumed varied from 435  kcal 
 to 670  kcal , with an energy composition of 4952% carbohydrate , 3640% fat , and 1112% 
 protein .
the subjects with sci were divided into the two groups [ hsci ( t56 ) and lsci ( t912 ) ] 
 according to the level of spinal cord injury .
the physiological characteristics ( age , body 
 weight , height , and bmi ) were compared among the three groups ( ab , hsci , and lsci ) by 
 one - way anova and dunnett s post hoc test . if either the normality or the equal variance 
 test failed , the kruskal - wallis test was performed .
the differences in the responses of 
 tef , plasma norepinephrine , and hr among the three groups were examined using two - way 
 anova with repeated measures ( one factor of time repetition ) .
if the main effect and 
 interaction were significant , the mean values at a given time were compared using 
 dunnett s post hoc test .
all statistical analyses were performed using 
 sigmaplot version 12.5 ( systat software , san jose , ca , usa ) .
the anthropometric characteristics of the three groups ( ab , hsci , and lsci ) are shown in 
 table 1 .
there were no significant differences 
 in age , body weight , height , and bmi among the three groups .
table 2table 2.resting energy expenditure , thermic effect of food , and meal size during the tef 
 studyab ( n=6)hsci ( n=3)lsci ( n=4)ree ( kcal / min)1.14  0.070.96  0.081.07  0.05postprandial ee ( kcal / min)1.51  0.091.15  0.121.34  0.05tef ( kcal for 2h)44.5  4.923.2  5.832.0  0.3adjusted tef against body weight0.59  0.050.36  0.06 * 0.49  0.04tef ( % meal)7.4  0.064.6  0.07 * 6.2  0.04meal size ( kcal)602.5  30.5501.7  55.3521.3
ree : resting energy expenditure ; tef : thermic effect of food 
 intake ; ab : able - bodied subjects ; sci : spinal cord injury ; hsci : higher thoracic sci 
 subjects ; lsci : lower thoracic sci subjects*significantly lower ( p<0.05 ) than ab shows the average data of the resting energy expenditure ( ree , kcal / min ) , 
 absolute and adjusted tef over 2 hours , and meal size of the three groups .
the adjusted tef 
 over 2 hours and tef ( % meal ) were significantly smaller ( p<0.05 ) in the hsci subjects 
 than in the ab subjects .
ree : resting energy expenditure ; tef : thermic effect of food 
 intake ; ab : able - bodied subjects ; sci : spinal cord injury ; hsci : higher thoracic sci 
 subjects ; lsci : lower thoracic sci subjects * significantly lower ( p<0.05 ) than ab the time courses of the average changes in absolute and adjusted tef following food intake 
 were compared among the three groups ( table 
 3table 3.the time courses of absolute tef and adjusted tef in the three groupsabsolute tef ( kcal)adjusted tef ( kcal / kg)60 min120 min180 min60 min120 min180 minab ( n=6)19.1  2.025.4  3.017.8  1.20.25  0.030.33  0.030.24  0.02hsci ( n=3)13.0  2.310.2  4.511.7  4.20.21  0.050.15  0.06 * 0.17  0.05lsci ( n=4)13.7  1.018.4  1.114.3  2.30.21  0.010.29  0.030.22
ab : able - bodied subjects ; sci : spinal cord injury ; hsci : higher thoracic sci 
 subjects ; lsci : lower thoracic sci subjects .
because the energy expenditure in one subject with hsci involved an artifact at 
 180  min , we removed his tef from pooled data at 180  min and did not perform 
 statistical analysis for the absolute and adjusted tef at 180  min . *
significantly lower ( p<0.05 ) than in ab ( two - way anova ) ) .
two - way anova of absolute tef indicated a significant main effect of time 
 ( p<0.05 ) , but not of group .
two - way anova of adjusted tef indicated significant main 
 effects of group and time .
post 
 hoc analyses revealed that the adjusted tef at 120  min was significantly smaller 
 in the hsci group than in the ab group , whereas the adjusted tef was the same in both the ab 
 and lsci groups .
ab : able - bodied subjects ; sci : spinal cord injury ; hsci : higher thoracic sci 
 subjects ; lsci : lower thoracic sci subjects .
because the energy expenditure in one subject with hsci involved an artifact at 
 180  min , we removed his tef from pooled data at 180  min and did not perform 
 statistical analysis for the absolute and adjusted tef at 180  min . *
significantly lower ( p<0.05 ) than in ab ( two - way anova ) table 4table 4.the time courses of plasma norepinephrine concentration and hr in the three 
 groupsnorepinephrine concentration ( ng / ml)hr ( bpm)baseline60 min120 min180 minbaseline60 min120 min180 minab ( n=6)0.33  0.050.43  0.080.33  0.050.47  0.1165.9  3.370.2  4.2 68.6  2.8 65.9  2.1hsci ( n=3)0.38  0.160.46  0.130.45  0.150.43  0.0765.2  2.575.7  7.0 76.2  8.1 70.2  4.2lsci ( n=4)0.44  0.020.54  0.050.50  0.020.45  0.0373.3  6.677.3  7.3 76.5  8.0 72.3  6.4data are shown in mean  sem .
ab : able - bodied subjects ; sci : spinal cord injury ; hsci : higher thoracic sci 
 subjects ; lsci : lower thoracic sci subjects .
significant differences from the resting value ( p<0.05 , two - way 
 anova ) shows the time courses of the postprandial changes in plasma norepinephrine 
 concentration and hr among the three groups .
two - way anova of norepinephrine levels 
 indicated no significant main effects of group or time .
two - way anova of hr identified a 
 significant main effect of time ( p<0.05 ) , but not of group .
in all the three groups , hr 
 had increased ( p<0.05 ) at 60  min and 120  min , compared to rest , but had returned to the 
 baseline level at 180  min .
ab : able - bodied subjects ; sci : spinal cord injury ; hsci : higher thoracic sci 
 subjects ; lsci : lower thoracic sci subjects .
the present study has examined whether the level of spinal cord injury affects the thermic 
 response to food intake .
the major findings of this study are that : 1 ) the adjusted tef at 
 60  min was the same among the subjects , irrespective of the presence or the absence of sci ; 
 2 ) the adjusted tef at 120  min was significantly smaller in the subjects with hsci than ab 
 subjects , but was not different between the lsci and ab subjects . taken together , it is 
 likely that thoracic sci at a lesion level t56 may decrease the thermic response to food 
 intake .
the obligatory component is the energy that 
 is required for nutrient digestion , absorption , transport , and storage
. it may be mainly 
 modulated by parasympathetic nervous system activity3 , 
 19 .
the facultative component , which 
 occurs in several tissues especially in skeletal muscles , is the energy spent in excess of 
 the obligatory requirements2,3,4 .
the energy expenditure in skeletal muscles 
 stimulated by an increase in muscle sna contributes substantially to the whole - body tef in 
 humans20 , 21 . despite a number of studies of the tef ,
the time courses of the 
 two components during the postprandial period remains to be established .
based on the time courses of the tef measured in this study , two possible conclusions can 
 be drawn from the differences in the adjusted tefs of the three groups ( ab , hsci , and lsci ) . 
 first , the adjusted tef at 60  min was not different among the three groups , suggesting that 
 the tef at 60  min may be mainly attributable to the obligatory component .
this conclusion 
 seems reasonable , because these all of the subjects had an intact parasympathetic nervous 
 system .
it is additionally supported by a previous finding that the obligatory thermogenesis 
 to food intake is not affected by the sci22 .
second , the adjusted tef at 120  min was blunted in hsci , compared 
 to ab , suggesting that the tef at 120  min may correspond to the facultative component , which 
 is influenced by sympathetic nervous system .
the adjusted tef at 120  min was not 
 significantly different between ab and lsci .
thus , it is conceivable that the extent of the 
 facultative component may depend on the level of injury .
the decreased sna due to the 
 sympathetic decentralization may affect , at least partly , the facultative component of the 
 subjects with hsci . another possible explanation for the reduction in the facultative component of adjusted tef 
 may be a decrease in the lean muscle mass . several studies have shown that tef is higher in 
 lean subjects than obese subjects , implying that skeletal muscle mass plays a role in 
 increasing energy expenditure after meal consumption13,14,15 . furthermore , astrup et al . suggested that the facultative tef 
 occurs mainly in skeletal muscles , while the contribution of fat tissues to facultative tef 
 is negligible2 , 21 .
based on these findings , it is likely that the amount of lean 
 muscle mass is an important physiological determinant of facultative tef . in sci ,
body 
 composition drastically changes with a loss of lean muscle mass as well as bone below the 
 level of injury and an increase in the total fat mass23 , 24 .
therefore , it is likely 
 that a decrease in lean muscle mass would result in a reduction in the facultative tef .
nevertheless , a significant difference was found in the changes in adjusted 
 tef , in addition , the present tef values were approximately the same as those previously 
 reported for sci25 .
second , the forearm 
 venous norepinephrine concentration may be an inaccurate measure of the influence of the 
 sympathetic decentralization of hsci and lsci on sna below the level of injury .
forearm 
 venous norepinephrine concentration may not reflect whole body sna but suggest regional 
 sna26 .
karlsson et al . found that leg 
 norepinephrine levels were significantly lower in sci subjects ( c7t4 ) than those in ab 
 subjects , while arm norepinephrine levels were almost the same27 .
third , we did not directly measure lean muscle mass , 
 although the amount of lean muscle mass is one of the important physiological determinants 
 of total tef .
fourth , we did not measure core body temperature in the subjects with sci . 

when drum temperature was measured in some ab subjects , drum temperature did not change 
 after food intake , suggesting that food - intake thermogenesis may not affect core body 
 temperature . finally
, we did not know whether all the six subjects with ais a had autonomic 
 complete dysfunction .
it is likely that thoracic sci at a lesion level of t56 causes a lower thermic response to 
 food intake due to sympathetic decentralization .
it is known that measured rmr is lower in 
 persons with tetraplegia and paraplegia than in ab subjects , probably due to decreased 
 sna22 .
thus , in addition to lower rmr , 
 reduced thermic response to food intake may also be a causative factor in the development of 
 obesity in sci , particular in hsci .
 [ purpose ] to investigate the influence of the level of spinal cord injury on the thermic 
 effect of food intake ( tef ) in persons with thoracic spinal cord injury . 
 [ subjects and 
 methods ] seven male subjects with spinal cord injury ( sci ; age , 40  6  years ) and six 
 able - bodied subjects ( ab ; age , 37  8  years ) volunteered to participate in the present 
 study . 
 the subjects consumed an identical test meal consisting of 7.9  kcal / kg of body 
 weight . 
 energy expenditure and plasma norepinephrine concentrations were measured over a 
 3-hour period . 
 [ results ] the adjusted tef at 60  min was almost the same among the three 
 groups [ ab , sci with high thoracic cord ( t56 ) injury ( hsci ) , and sci with low thoracic 
 cord ( t912 ) injury ( lsci ) ] . 
 although the lsci group had almost the same adjusted tef at 
 120  min as the ab group , the adjusted tef at 120  min of the hsci group was significantly 
 lower than that of the ab group . 
 the changes in plasma norepinephrine concentration and 
 heart rate in response to food intake were similar among the three groups . 
 [ conclusion ] 
 sci at the t56 level results in a lower tef due to sympathetic decentralization . 
INTRODUCTION
SUBJECTS AND METHODS
RESULTS
DISCUSSION