2 Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110; and 1 Department of Medicine, University College London Medical School, London N19 3UA, United Kingdom
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ABSTRACT |
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We evaluated whole body and regional
(subcutaneous abdominal adipose tissue and forearm) norepinephrine (NE)
kinetics in seven lean (body mass index 21.3 ± 0.5 kg/m2) and six upper body obese
(body mass index 36.4 ± 0.4 kg/m2) women who were matched on
fat-free mass. NE kinetics were determined by infusing
[3H]NE and obtaining
blood samples from a radial artery, a deep forearm vein draining mostly
skeletal muscle, and an abdominal vein draining subcutaneous abdominal
fat. Mean systemic NE spillover tended to be higher in obese (2.82 ± 0.49 nmol/min) than in lean (2.53 ± 0.40 nmol/min) subjects,
but the differences were not statistically significant. Adipose tissue
and forearm NE spillover rates into plasma were greater in lean (0.91 ± 0.08 pmol · 100 g
tissue1 · min
1
and 1.01 ± 0.09 pmol · 100 ml
tissue
1 · min
1,
respectively) than in obese (0.26 ± 0.05 pmol · 100 g
tissue
1 · min
1
and 0.58 ± 0.11 pmol · 100 ml
tissue
1 · min
1,
respectively) subjects (P < 0.01).
These results demonstrate that adipose tissue is an active site for NE
metabolism in humans. Adipose tissue NE spillover is considerably lower
in obese than in lean women, which may contribute to the lower rate of
lipolysis per kilogram of fat mass observed in obesity.
catecholamines; obesity; energy metabolism
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INTRODUCTION |
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THE SYMPATHETIC NERVOUS SYSTEM (SNS) is an important regulator of energy metabolism because of its effect on both energy expenditure and energy mobilization. Therefore, SNS activity may be important in the etiology and pathophysiology of obesity. A decrease in SNS activity contributes to the onset of obesity in certain animal models (6) and may also contribute to the onset of obesity in humans (34). It is not clear whether SNS activity is altered in persons who are already obese, because of conflicting results from more than 40 different studies (38). However, the data from most studies suggest that whole body SNS activity, measured as plasma norepinephrine (NE) concentration, urinary NE excretion, or systemic NE spillover rate into plasma, is either the same in lean and obese subjects or increases with increasing adiposity. Skeletal muscle SNS activity, measured by microneurography, increases with increasing body fat mass (14, 15, 27, 31). Therefore, it is possible that regional heterogeneity in SNS activity may be responsible for some of the variability observed between studies.
A better understanding of regional SNS activity may have important clinical implications in obesity. An increase in SNS activity in specific tissues may be involved in the pathogenesis of some of the medical complications of obesity, such as hypertension (36) and cardiovascular disease (24). A decrease in adipose tissue SNS activity could be responsible for the lower rates of lipolysis per kilogram of adipose tissue reported in obese compared with lean subjects (18). Alterations in regional SNS activity are likely to occur during obesity therapy, which usually involves decreasing energy intake and increasing physical activity. Hypocaloric dieting or fasting decreases muscle SNS activity, which conserves energy (21, 29, 39), whereas exercise increases SNS activity, which stimulates the release of free fatty acids and glycerol from adipose tissue to provide fuel for working muscles and gluconeogenic precursors for the liver (17, 26).
The SNS influences metabolic processes through nerves that innervate different body tissues. NE is synthesized and stored in sympathetic nerve endings and is the neurotransmitter involved in SNS signal transmission (4). Although most of the NE released from sympathetic postganglionic neurons is cleared locally by neuronal reuptake and effector cell metabolism, a portion of released NE spills over into the bloodstream. Therefore, whole body NE spillover rate into plasma has been used as an index of SNS activity. However, whole body NE spillover represents total spillover from sympathetic neurons in many tissues and NE release into plasma from the adrenal medullas and, thus, does not provide information on SNS activity in specific tissues. The use of tracer methodology in conjunction with arteriovenous balance permits the assessment of regional NE spillover by individual tissues.
In the present study, we evaluated whole body and regional (subcutaneous abdominal adipose tissue and forearm) NE kinetics in lean and obese women by infusing [3H]NE and catheterizing the radial artery, a deep forearm vein draining mostly skeletal muscle, and an abdominal vein draining subcutaneous abdominal fat. We hypothesized that whole body and forearm NE spillover rates would be greater, whereas adipose tissue NE spillover rates would be lower, in obese than in lean subjects.
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MATERIALS AND METHODS |
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Subjects. Seven lean (28 ± 2.1 yr) and six upper body obese (waist-to-hip circumference ratio >0.85 and waist circumference >100 cm; 38 ± 3.1 yr) white women (Table 1) participated in this study, which was approved by the Institutional Review Board, the Radioactive Drug Research Committee, and the General Clinical Research Center of Washington University School of Medicine. All subjects gave informed written consent. Lean and obese women were matched for fat-free mass (FFM), as determined by dual-energy X-ray absorptiometry (Hologic QDR 1000/W, Waltham, MA) 5 to 7 days before the isotope infusion study. Subjects were nonsmokers, were weight stable for at least 2 mo before the study, and were not taking any medications. All subjects performed normal daily activities, such as shopping, driving, and walking short distances, but none participated in regular aerobic exercise, such as walking, jogging, or cycling. Subjects were considered to be healthy after a history and physical examination, blood tests, a 2-h oral glucose tolerance test, and an electrocardiogram.
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Study protocol. Subjects were admitted
to the General Clinical Research Center in the evening before the
isotope infusion study within the first 2 wk of the follicular phase of
the menstrual cycle of each subject. All lean subjects consumed an
evening meal containing 12 kcal/kg body wt, and all obese subjects
consumed an evening meal containing 12 kcal/kg adjusted body wt, where adjusted body weight was calculated as ideal body weight + [(actual body weight ideal body weight)(0.25)]. At
precisely 2000, subjects ingested a liquid formula snack containing 40 g carbohydrate, 6.1 g fat, and 8.8 g protein (Ensure, Ross
Laboratories, Columbus, OH).
The following morning, after subjects fasted overnight, catheters were inserted into a forearm vein for isotope infusion and into a radial artery, a deep forearm vein (usually the median cubital vein), and an abdominal vein (draining subcutaneous abdominal adipose tissue) (10) for blood sampling. The tip of the abdominal vein catheter was placed just above the inguinal ligament; the deep vein catheter was inserted retrogradely in a deep forearm vein and positioned so that neither the catheter tip itself nor a fluid thrill from a bolus infusion into the deep vein was palpable.
At 0900, a constant infusion (10 nCi · kg1 · min
1)
of
levo-[ring-2,5,6-3H]NE
(40-60 Ci/mmol; New England Nuclear, Boston, MA) was started and
continued for 30 min. An arterial blood sample was obtained before
isotope infusion to determine background NE specific activity. Blood
samples were obtained from artery and deep forearm and abdominal veins
simultaneously every 5 min between 0920 and 0930 (at 20, 25, and 30 min
of labeled NE infusion). Two minutes before each deep forearm venous
blood sample, a wrist pressure cuff was insufflated to 180 mmHg to
exclude blood draining from the hand.
Abdominal subcutaneous adipose tissue blood flow (ATBF) was measured by the 133Xe-clearance technique (19). Approximately 100 Ci of 133Xe dissolved in 0.15 ml of normal saline was slowly injected over 60 s into subcutaneous adipose tissue, 3 cm lateral to the umbilicus. A cesium iodide detector (Oakfield Instruments, Eynsham, UK) was placed over the site of injection, and the decline in 133Xe counts was determined between 0930 and 0945 (25), which was at least 60 min after the injection of 133Xe. Forearm blood flow was determined by mercury strain-gauge plethysmography (Hokanson, Bellevue, WA) (12) every 5 min between 0930 and 0945. The forearm was elevated 10-15 cm above the right atrium. The wrist cuff was inflated to a suprasystolic level 1 min before and during measurement to exclude hand blood flow from the arm flow measurement, and the arm cuff was inflated to 40 mmHg to occlude venous outflow during measurement. The four flow measurements were averaged to determine overall forearm blood flow.
Analyses. Plasma NE concentration was determined by a single isotope derivative radioenzymatic method, and plasma [3H]NE specific activity was determined after organic extraction as described previously (30).
Calculations. Physiological and isotopic steady states were present during the last 15 min of isotope infusion as determined by constant NE concentration and [3H]NE specific activity, so Steele's equation for steady-state conditions was used to calculate whole body NE kinetics (32)
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The systemic metabolic clearance rate for NE (in ml/min) was calculated as NE spilloversyst divided by plasma NE concentration.
Local tissue NE clearance rate (in ml · unit of
tissue1 · min
1)
was calculated as local NE tissue extraction times plasma flow (37) and
assumes that NE is only carried in plasma (11)
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Subcutaneous ATBF was determined by measuring the rate of removal of
133Xe from adipose tissue by using
a monoexponential decay and an adipose tissue-to-blood partition
coefficient for Xe (between 1 ml of blood and 100 g of tissue) of 10 ml/g (1). Therefore, blood flow is expressed as milliliters of blood
per 100 g of adipose tissue per minute. Subcutaneous adipose tissue
plasma flow was calculated as ATBF × (1 hematocrit).
Forearm blood flow was determined by plethysmography, which measures
the rate of change in limb volume and is expressed as milliliters of
blood per 100 ml of forearm per minute. Forearm plasma flow was
calculated as forearm blood flow × (1
hematocrit).
Local NE spillover from adipose tissue and forearm was calculated as (11)
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Statistical analyses. Student's
two-tailed t-test for independent
samples was used to test the significance of differences between lean
and obese groups. A P value of
0.05 was considered to be statistically significant. All data are
means ± SE.
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RESULTS |
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Systemic NE kinetics. Arterial plasma
NE concentrations and systemic NE kinetics are shown in Table
2. Mean systemic NE spillover was similar
in lean and obese subjects, and the slight trend toward increased
systemic NE spillover in the obese group was not statistically significant (P = 0.66).
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Adipose tissue NE kinetics. Mean
subcutaneous adipose tissue venous plasma NE concentrations were
similar to arterial values in both lean (0.80 ± 0.08 and 0.88 ± 0.08 nmol/ml for abdominal vein and artery, respectively) and obese
(0.73 ± 0.07 and 0.93 ± 0.09 nmol/ml for abdominal vein and
artery, respectively) subjects. ATBF was greater in lean than obese
subjects (3.99 ± 0.71 and 1.54 ± 0.22 ml · 100 g
tissue1 · min
1,
respectively; P < 0.05).
Subcutaneous adipose tissue NE spillover was threefold greater in lean
(0.91 ± 0.08 pmol · 100 g
tissue
1 · min
)
than in obese (0.26 ± 0.05 pmol · 100 g
tissue
1 · min
1
) subjects (P < 0.01) (Fig.
1). Clearance of plasma NE by adipose tissue was also
greater in lean (1.41 ± 0.13 ml · 100 g
tissue
1 · min
1)
than obese (0.61 ± 0.12 ml · 100 g
tissue
1 · min
1)
subjects (P < 0.05; Fig. 1).
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Forearm NE kinetics. Deep venous
plasma NE concentrations were greater than arterial values in all
subjects, demonstrating net NE release by forearm tissue. Forearm blood
flow was greater in lean than obese subjects (2.31 ± 0.29 and 1.06 ± 0.14 ml · 100 ml
tissue1 · min
1,
respectively; P < 0.05). Forearm NE spillover was greater in lean
(1.01 ± 0.09 pmol · 100 ml
tissue
1 · min
1)
than in obese (0.58 ± 0.11 pmol · 100 ml
tissue
1 · min
1)
subjects (P < 0.01) (Fig.
2). Clearance of plasma NE by
forearm tissue was also greater in lean (0.92 ± 0.11 ml · 100 ml
1 · min
1)
than in obese (0.42 ± 0.05 ml · 100 ml
1 · min
1)
subjects (P < 0.001) (Fig. 2).
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DISCUSSION |
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In the present study, we evaluated whole body and regional (subcutaneous abdominal adipose tissue and forearm) NE kinetics in vivo in lean and obese women, who were closely matched for fat-free body mass. The most important new finding of this study is the marked difference in adipose tissue NE metabolism found in lean and obese women; NE spillover and clearance rates in subcutaneous abdominal adipose tissue (expressed per 100 g of fat mass) were considerably lower in obese than in lean subjects. This decrease in adipose tissue NE kinetics (an index of SNS activity) may be an important mechanism for downregulating basal adipose tissue lipolysis in obese persons. Compared with lean subjects, lipolytic rates per kilogram of fat mass are decreased in obese subjects, whereas whole body lipolysis or lipolytic rates per kilogram of lean body mass are often increased because of the large increase in body fat mass (13, 18). Therefore, decreased adipose tissue lipolysis in obese persons may have clinical benefits by preventing even greater increases in whole body lipolytic rates. Excessive lipolysis and free fatty acid release into plasma could have adverse metabolic effects on hepatic very low density lipoprotein production and plasma lipid concentrations (20), hepatic glucose production (9), and peripheral glucose uptake (35).
In comparison with the lean group, forearm NE spillover rate, an index of skeletal muscle SNS activity, was lower in the obese subjects. These results differ from previous studies (14, 15, 27, 30), which found muscle sympathetic nerve activity increased with increasing adiposity. It is possible that differences in methodologies between these studies and ours may be responsible for the different results. The previous studies determined leg muscle SNS activity by microneurography (14, 15, 27, 31), whereas we used a combination of tracer and arteriovenous balance methodologies to assess forearm NE spillover. The advantages and disadvantages of each method for assessing SNS activity have been carefully reviewed (10). It is possible that sympathetic nerve impulses, which are measured by microneurography, do not cause the same amount of NE release in lean and obese subjects. Indeed, data from a recent study (16) suggest that results obtained by microneurography may correlate poorly with regional skeletal muscle NE spillover. Moreover, in the two studies that evaluated skeletal muscle SNS activity by microneurography in women, values for obese subjects who had similar body mass index or percent body fat as our obese group were within the range of values reported among women who had the same body mass index or percent body fat as our lean group (15, 27). It is also likely that the presence of increased forearm subcutaneous and intermuscular fat contributed to the low rate of forearm NE spillover measured in our obese subjects because of the low rate of NE spillover in fat tissue.
We used subcutaneous abdominal adipose tissue NE spillover as an index of body fat SNS activity and forearm NE spillover as an index of skeletal muscle SNS activity. However, sympathetic outflow to different peripheral tissues is not uniform (38), and it is also likely that heterogeneity in SNS activity also exists within similar tissues located at different sites. Although skeletal muscle SNS activity measured by microneurography during basal conditions has been found to be similar in arm and leg muscle beds (3, 23, 33), Karlsson et al. (16) found that muscle SNS activity measured by NE spillover was twofold greater in arms than in legs. SNS activity in adipose tissue depots has not previously been studied. Nonetheless, if we assume that our regional results are representative of similar tissues throughout the body, our data suggest that skeletal muscle and adipose tissue combined account for only a small portion of whole body NE spillover rate. Therefore, most of the NE released into the circulation comes from other tissues. Other investigators have found that NE spillover from the lungs, kidneys, heart, and splanchnic bed accounted for approximately two-thirds of total spillover (8), whereas both upper and lower extremities constituted only 7% of total spillover (16).
Systemic (whole body) NE spillover rates in our obese subjects were similar to values observed in the lean group. We are aware of three other studies that have evaluated the relationship between adiposity and systemic NE spillover in humans (5, 22, 28). One study (5) found marginally lower systemic NE spillover rates in obese compared with lean subjects, whereas the other two studies (22, 28) found a direct positive correlation between adiposity and systemic NE spillover. It is possible that by carefully controlling lean body mass we minimized differences in systemic NE spillover between our lean and obese groups. Although we cannot exclude the possibility that the trend toward an increase in systemic NE spillover rate in the obese group would be statistically significant had we studied more subjects, the possibility of a type II statistical error is unlikely. Approximately 180 subjects would be needed in each group to make the differences in systemic NE spillover rate that we observed between lean and obese women statistically significant at a P value of 0.05 with a power of 0.8.
In a review of more than 40 studies that evaluated SNS activity in lean and obese subjects, considerable diversity was found in results between studies (38). As noted above for data on whole body NE spillover, measures of plasma NE and epinephrine concentration and urinary NE and epinephrine excretion were lower, the same, and higher in obese compared with lean subjects. Some of the variability in these studies may be related to confounding variables that influence SNS activity. In the present study, careful attention was made to eliminate as many factors as possible that are known to affect SNS activity (38). Lean and obese subjects were matched by gender, antecedent diet, physical activity history, and lean body mass. In addition, no subject had hypertension or abnormal glucose tolerance, which is associated with alterations in SNS activity (2, 3).
The use of tracer methodology to determine whole body NE spillover measures a summation of NE released into plasma from SNS activity in different tissues and from NE secretion by the adrenal medullas. The combined use of tracer methodology and arteriovenous balance eliminates the contribution of NE from the adrenal medullas. However, regional NE entering plasma represents only a portion of NE released by sympathetic neurons. Most of the NE is cleared by sympathetic neuronal reuptake and storage or metabolism by monoamine oxidase and by effector cell uptake and metabolism by catechol-O-methyltransferase (4). Spillover of NE from tissue into plasma depends on the number and firing rate of local sympathetic nerve terminals, capillary permeability, and the efficiency of neuronal reuptake and effector cell clearance mechanisms (cf. Ref. 11). In addition, regional blood flow can influence NE spillover because it can affect the concentration gradient between interstitial and plasma NE. Therefore, it is possible, but we believe unlikely, that differences in tissue blood flow between our lean and obese subjects contributed to the differences we observed in local NE spillover. Regional adipose tissue and forearm NE kinetics were still significantly different between lean and obese subjects when we recalculated our data by using Chang's equation for regional plasma NE appearance rate (7), which is not affected by tissue blood flow. Finally, because the anatomic distribution of sympathetic neurons within adipose and forearm tissues is not known, we cannot determine whether NE released into plasma reflects activity of sympathetic neurons innervating predominantly adipocytes in adipose tissue, myocytes in forearm tissue, local vascular structures in each tissue, or a combination of these effector cells.
In summary, the results of the present study demonstrate that subcutaneous adipose tissue is an active site for NE metabolism in humans. Moreover, adipose tissue NE spillover was considerably lower in obese than in lean subjects, which may be an important contributor to the lower rate of lipolysis per kilogram of fat mass observed in obesity.
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ACKNOWLEDGEMENTS |
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We thank Renata Braudy and the nursing staff of the General Clinical Research Center for help in performing the experimental protocols and Dr. Guohong Zhao and Wei-qing Feng for technical assistance.
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FOOTNOTES |
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This study was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-49989, General Clinical Research Center Grant RR-00036, and by The Wellcome Trust.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Address for reprint requests: S. Klein, Washington Univ. School of Medicine, 660 S. Euclid Ave., Box 8127, St. Louis, MO 63110-1093.
Received 2 April 1998; accepted in final form 4 August 1998.
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REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Anderson, A. M.,
and
J. Ladefoged.
Partition coefficient of 133Xenon between various tissues and blood in vivo.
Scand. J. Clin. Lab. Invest.
19:
72-78,
1967[Medline].
2.
Anderson, E. A.,
C. A. Sinkey,
W. J. Lawton,
and
A. L. Mark.
Elevated sympathetic nerve activity in borderline hypertensive humans. Evidence from direct intraneural recordings.
Hypertension
14:
177-183,
1989[Abstract].
3.
Astrup, A. V.,
N. J. Christensen,
and
L. Breum.
Reduced plasma noradrenaline concentrations in simple-obese and diabetic obese patients.
Clin. Sci. (Colch.)
80:
53-58,
1991[Medline].
4.
Axelrod, J.,
and
R. Weinshilboum.
Catecholamines.
N. Engl. J. Med.
287:
237-243,
1972[Medline].
5.
Bazelmans, J.,
P. Nestel,
K. O'Dea,
and
M. Esler.
Blunted norepinephrine responsiveness to changing energy states in obese subjects.
Metabolism
34:
154-160,
1985[Medline].
6.
Bray, G. A.,
D. A. York,
and
J. S. Fisler.
Experimental obesity: a homeostatic failure due to defective nutrient stimulation of the sympathetic nervous system.
Vitam. Horm.
45:
1-125,
1989[Medline].
7.
Chang, P. C.,
E. Krick,
J. A. Van der Krogt,
and
P. Van Brummelen.
Does regional norepinephrine spillover represent local sympathetic activity?
Hypertension
18:
56-66,
1991[Abstract].
8.
Esler, M.,
G. Jennings,
P. Korner,
P. Blombery,
N. Sacharias,
and
P. Leonard.
Measurement of total and organ-specific norepinephrine kinetics in humans.
Am. J. Physiol.
247 (Endocrinol. Metab. 10):
E21-E28,
1984
9.
Ferrannini, E.,
E. J. Barrett,
S. Bevilacqua,
and
R. A. DeFronzo.
Effect of fatty acids on glucose production and utilization in man.
J. Clin. Invest.
72:
1737-1747,
1983[Medline].
10.
Frayn, K. N.,
S. W. Coppack,
S. M. Humphreys,
and
P. L. Whyte.
Metabolic characteristics of human adipose tissue in vivo.
Clin. Sci. (Colch.)
76:
509-516,
1989[Medline].
11.
Goldstein, D. S.
Clinical assessment of catecholamine function.
In: Stress, Catecholamines, and Cardiovascular Disease. New York: Oxford University, 1995, p. 234-286.
12.
Greenfield, A. D. M.,
R. J. Whitney,
and
J. F. Mowbray.
Methods for the investigation of peripheral blood flow.
Br. Med. Bull.
19:
101-109,
1963.
13.
Jensen, M. D.,
M. W. Haymond,
R. A. Rizza,
P. E. Cryer,
and
J. M. Miles.
Influence of body fat distribution on free fatty acid metabolism in obesity.
J. Clin. Invest.
83:
1168-1173,
1989[Medline].
14.
Jones, P. P.,
K. P. Davy,
S. Alexander,
and
D. R. Seals.
Age-related increase in muscle sympathetic nerve activity is associated with abdominal adiposity.
Am. J. Physiol.
272 (Endocrinol. Metab. 35):
E976-E980,
1997
15.
Jones, P. P.,
S. Snitker,
J. S. Skinner,
and
E. Ravussin.
Gender differences in muscle sympathetic nerve activity: effect of body fat distribution.
Am. J. Physiol.
270 (Endocrinol. Metab. 33):
E363-E366,
1996
16.
Karlsson, A.-K.,
M. Elam,
P. Lonnroth,
L. Sullivan,
and
P. Friberg.
Differentiated norepinephrine spillover in human skeletal muscle.
Am. J. Physiol.
273 (Regulatory Integrative Comp. Physiol. 42):
R16-R21,
1997
17.
Klein, S.,
E. F. Coyle,
and
R. R. Wolfe.
Fat metabolism during low-intensity exercise in endurance-trained and untrained men.
Am. J. Physiol.
267 (Endocrinol. Metab. 30):
E934-E940,
1994
18.
Klein, S.,
V. R. Young,
G. L. Blackburn,
B. R. Bistrian,
and
R. R. Wolfe.
The impact of body composition on the regulation of lipolysis during short-term fasting.
J. Am. Coll. Nutr.
7:
77-84,
1988[Abstract].
19.
Larsen, O. A.,
N. A. Lassen,
and
F. Quaade.
Blood flow through human adipose tissue determined with radioactive xenon.
Acta Physiol. Scand.
66:
337-345,
1966[Medline].
20.
Lewis, G. F.,
K. D. Uffelman,
L. W. Szeto,
B. Weller,
and
G. Steiner.
Interaction between free fatty acids and insulin in the acute control of very low density lipoprotein production in humans.
J. Clin. Invest.
95:
158-166,
1995[Medline].
21.
O'Dea, K.,
M. Esler,
P. Leonard,
J. Stockigt,
and
P. Nestel.
Noradrenaline turnover during under- and over-eating in normal weight subjects.
Metabolism
31:
896-899,
1982[Medline].
22.
Poehlman, E. T.,
A. W. Gardner,
M. I. Goran,
P. J. Arciero,
M. J. Toth,
P. A. Ades,
and
J. Calles-Escando.
Sympathetic nervous system activity, body fatness, and body fat distribution in younger and older males.
J. Appl. Physiol.
78:
802-806,
1995
23.
Rea, R.,
and
B. G. Wallin.
Sympathetic activity in arm and leg muscles during lower body negative pressure in humans.
J. Appl. Physiol.
66:
2778-2781,
1989
24.
Rowe, J.,
and
B. Troen.
Sympathetic nervous system and aging in man.
Endocr. Rev.
1:
167-179,
1980[Medline].
25.
Samra, J. S.,
K. N. Frayn,
J. A. Giddings,
M. L. Clark,
and
I. A. Macdonald.
Modification and validation of a commercially available portable detector for measurement of adipose tissue blood flow.
Clin. Physiol.
15:
241-248,
1995[Medline].
26.
Savard, G.,
S. Strange,
B. Kiens,
E. A. Richter,
N. J. Christensen,
and
B. Saltin.
Noradrenaline spillover during exercise in active versus resting skeletal muscle in man.
Acta Physiol. Scand.
131:
507-515,
1987[Medline].
27.
Scherrer, U.,
D. Randin,
L. Tappy,
P. Vollenweider,
E. Jequier,
and
P. Nicod.
Body fat and sympathetic nerve activity in healthy subjects.
Circulation
89:
2634-2640,
1994[Abstract].
28.
Schwartz, R.,
L. Jaeger,
and
R. Veith.
The importance of body composition to the increase in plasma norepinephrine appearance rate in elderly men.
J. Gerontol.
42:
546-551,
1987[Medline].
29.
Schwartz, R. S.,
L. F. Jaeger,
R. C. Veith,
and
S. Lakshminarayan.
The effect of diet or exercise on plasma norepinephrine kinetics in moderately obese young men.
Int. J. Obes.
14:
1-11,
1990[Medline].
30.
Shah, S.,
W. E. Clutter,
and
P. E. Cryer.
External and internal standards in the single isotope derivative (radioenzymatic) assay of plasma norepinephrine and epinephrine in normal humans and patients with diabetes or chronic renal failure.
J. Lab. Clin. Med.
106:
624-629,
1985[Medline].
31.
Spraul, M.,
E. Ravussin,
A. M. Fontvieille,
R. Rising,
D. E. Larson,
and
E. A. Anderson.
Reduced sympathetic nervous activity. A potential mechanism predisposing to body weight gain.
J. Clin. Invest.
92:
1730-1735,
1993[Medline].
32.
Steele, R.
Influences of glucose loading and of injected insulin on hepatic glucose output.
Ann. NY Acad. Sci.
82:
420-430,
1959.
33.
Sundlof, G.,
and
B. G. Wallin.
The variability of muscle nerve sympathetic activity in resting recumbent man.
J. Physiol. (Lond.)
272:
383-397,
1977[Medline].
34.
Tataranni, P.,
J. Young,
C. Bogardus,
and
E. Ravussin.
A low sympathoadrenal activity is associated with body weight gain and development of central adiposity in Pima Indian men.
Obes. Res.
5:
341-347,
1997[Abstract].
35.
Thiebaud, D.,
R. A. DeFronzo,
E. Jacot,
A. Golay,
K. Acheson,
E. Maeder,
E. Jequier,
and
J.-P. Felber.
Effect of long chain triglyceride infusion on glucose metabolism in man.
Metabolism
31:
1128-1136,
1982[Medline].
36.
Tuck, M. L.
Obesity, the sympathetic nervous system, and essential hypertension.
Hypertension
19:
67-77,
1992.
37.
Wolfe, R. R.
Tracers in Metabolic Research: Radioactive and Stable Isotope Tracers in Biomedicine. New York: Wiley-Liss, 1992, p. 261-263.
38.
Young, J. B.,
and
I. A. MacDonald.
Sympathoadrenal activity in human obesity: heterogeneity of findings since 1980.
Int. J. Obes.
16:
959-967,
1992.
39.
Young, J. B.,
R. M. Rosa,
and
L. Landsberg.
Dissociation of sympathetic nervous system and adrenal medullary responses.
Am. J. Physiol.
247 (Endocrinol. Metab. 10):
E35-E40,
1984