0021-972X/98/$03.00/0
Journal of Clinical Endocrinology and Metabolism
Copyright © 1998 by The Endocrine Society
Vol. 83, No. 11
Printed in U.S.A.
Respiratory Quotient Is Inversely Associated with
Muscle Sympathetic Nerve Activity
SØREN SNITKER, P. ANTONIO TATARANNI,
AND
ERIC RAVUSSIN
Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney
Diseases, National Institutes of Health, Phoenix, Arizona 85016
ABSTRACT
The relative amounts of the macronutrients oxidized by an individual are reflected in the respiratory quotient (RQ), which varies
inversely with lipid oxidation. A high RQ, indicating a relatively low
lipid oxidation, and a low activity of the sympathetic nervous system
have both been identified as risk factors for body weight gain. The
stimulatory effect of norepinephrine on lipid oxidation suggests that
low lipid oxidation may contribute to the relationship between low
sympathetic nervous activity and body weight gain. The purpose of
the present study was to determine whether low basal muscle sympathetic nerve activity (MSNA), a direct measure of sympathetic
nervous outflow, is independently associated with low lipid oxidation.
Intraneural recordings of basal MSNA were performed in 39 healthy,
nondiabetic males, 19 Caucasians (mean 6SD, 33 6 9 yr, 91 6 23 kg,
and 28 6 11% body fat) and 20 Pima Indians (30 6 5 yr, 94 6 25 kg,
and 35 6 8% fat) immediately after measurement of 24-h RQ in a
respiratory chamber. Basal MSNA, energy balance, and age were
independent determinants of 24-h RQ, together explaining 45% of its
variability. Accordingly, 24-h RQ adjusted for energy balance and age
was inversely related to MSNA (r 5 20.41; P 5 0.01). Race, percent
body fat, and fasting plasma insulin were not independent determinants of 24-h RQ. Although MSNA explained only a limited part of the
variability in 24-h RQ, the results support the hypothesis that an
effect on lipid oxidation contributes to the demonstrated relationship
between low activity of the sympathetic nervous system and body
weight gain. (J Clin Endocrinol Metab 83: 3977–3979, 1998)
O
the Gila River Indian Community. All subjects gave written informed
consent.
BESITY is associated with a high risk of potentially fatal
diseases (1). To devise more successful therapies for
obesity than those currently offered, further insight into the
regulation of body weight is needed. When controlling for
other factors, a high respiratory quotient (RQ), i.e. a low lipid
relative to carbohydrate oxidation, is an established risk factor for weight gain (2, 3) and is a heritable trait (2). The
physiological background for individual differences in substrate oxidation and RQ is not well understood. Because the
sympathetic nervous system has a stimulatory effect on lipid
oxidation, as demonstrated by pharmacological intervention
(4, 5), and a low sympathetic nervous system activity has
been identified as a predictor of weight gain (6), it is conceivable that a low sympathetic nervous activity may be a
contributing factor to a low lipid oxidation.
The objective of the present study was to test whether 24-h
RQ is related to basal sympathetic nervous activity in Pima
Indian and Caucasian males.
Subjects and Methods
Twenty Pima Indian and 19 Caucasian healthy men were studied
(Table 1). Subjects were admitted to the NIH Clinical Research Unit in
Phoenix, AZ, and were fed a weight maintenance diet (50% carbohydrate, 30% fat, and 20% protein). Sodium intake was 4 – 6 g/day. All
subjects were healthy by clinical examination and screening blood tests
and were nondiabetic according to WHO criteria (7). Body composition
was determined by dual energy x-ray absorptiometry (DPX-1, Lunar
Radiation Corp., Madison, WI) (8). Waist and thigh circumferences were
measured as previously described (9). The study was approved by the
NIDDK/NIAMS Institutional Review Board and the Tribal Council of
RQ
After 4 days or more on the weight maintenance diet, the subject spent
23 h in a respiratory chamber as previously described (10). The energy
content of the diet provided in the chamber was about 20% lower than
that of the weight maintenance diet to accommodate the reduction in
physical activity. RQ was calculated as the ratio between CO2 produced
and O2 consumed for the duration of the stay. Energy balance was
calculated by subtracting 24-h energy expenditure (10) from actual energy intake and was expressed as a percentage of 24-h energy expenditure. No exercise was allowed.
Sympathetic nervous system activity
Immediately after the stay in the respiratory chamber, basal muscle
sympathetic nerve activity (MSNA) was recorded as previously described (9) while the subject was in the supine position. MSNA was
identified visually and expressed as the mean number of bursts per min
over a 10-min period. All scoring was performed in duplicate by two
experienced individuals who were blinded to the subjects’ characteristics and whose scorings have inter- and intraindividual variabilities
around 5% for individual minutes (11).
Statistical analysis
Data were analyzed using SAS software (SAS Institute, Inc., Cary,
NC). Relationships between variables were determined by Spearman’s
product-moment correlation and linear regression analysis as indicated.
Adjusted values were calculated by adding residuals (from linear regression analysis) to the group means.
Results
Received April 16, 1998. Revision received July 30, 1998. Accepted
August 6, 1998.
Address all correspondence to: Søren Snitker, M.D., Ph.D., National
Institutes of Health, 4212 North 16th Street, Room 541, Phoenix, Arizona
85016. E-mail: [email protected].
Mean values of basal MSNA, 24-h RQ, and energy balance
are given by race in Table 2. MSNA was correlated with
percent body fat in each group (r 5 0.47, P 5 0.04 in Caucasians; r 5 0.70, P 5 0.006 in Pima Indians), but independent
3977
3978
TABLE 2. Energy metabolism and muscle sympathetic nerve
activity results
TABLE 1. Characteristics of the subjects
Age (yr)
Wt (kg)
Ht (cm)
% Body fat
Waist/thigh ratio
Fasting plasma glucose
(mg/dL)
2-h plasma glucose
(mg/dL)a
Fasting plasma insulin
(mU/mL)
2-h plasma insulin
(mU/mL)a
JCE & M • 1998
Vol 83 • No 11
SNITKER, TATARANNI, AND RAVUSSIN
Caucasians
(n 5 19)
P
Pima Indians
(n 5 20)
33 6 9
91 6 23
178 6 7
28 6 11
1.51 6 0.13
82 6 11
NS
NS
,0.005
,0.05
,0.05
NS
30 6 5
94 6 25
172 6 6
35 6 8
1.64 6 0.18
83 6 12
98 6 38
NS
113 6 26
8.5 6 4.1
,0.01
17.2 6 2.5
58 6 43
NS
108 6 84
Energy intake (Cal/day)a
24-h energy expenditure
(Cal/day)
Energy balance (%)b
24-h RQ
Muscle sympathetic nerve
activity (bursts/min)
Caucasians
P
Pima Indians
2280 6 320
2370 6 290
NS
NS
2390 6 380
2400 6 310
23.3 6 12.1
0.85 6 0.02
29 6 12
NS
NS
NS
20.2 6 13.1
0.85 6 0.02
26 6 12
Values are the mean 6 SD.
a
Actual energy intake while in the chamber.
b
Expressed as a percentage of energy expenditure.
Values are the mean 6 SD.
a
Two hours after a 75-g glucose load.
of percent body fat, basal MSNA was, on the average, 8 6 5
bursts/min lower (mean 6 sd; P 5 0.04) in Pima Indians than
in Caucasians (Fig. 1). In a linear regression model in which
the other independent variables were percent body fat and
race, the interaction term between percent body fat and race
was not a significant determinant of basal MSNA, indicating
that the slopes of the regression lines between basal MSNA
and percent body fat were similar in Pima Indians and Caucasians. Multiple linear regression analyses indicated that
basal MSNA (P 5 0.01), energy balance (P 5 0.002), and age
(P 5 0.04) were significant independent determinants of 24-h
RQ, explaining 45% of its variability, whereas race, percent
body fat, waist/thigh ratio, and fasting plasma insulin concentration were not. To graphically represent the appropriate
linear regression model, the relationship between 24-h RQ,
adjusted for energy balance and age, and basal MSNA is
shown in Fig. 2. In agreement with the linear regression
model, these two variables were negatively correlated (r 5
20.41; P 5 0.01), indicating that 17% of the variability in 24-h
RQ could be attributed to MSNA. When the races were
considered separately, the effect of basal MSNA on 24-h RQ
independent of energy balance and age was significant in
Caucasians (P 5 0.03), but not in Pima Indians (P 5 0.19).
However, in a linear regression model, in which the independent variables were MSNA, energy balance, age, and
race, the interaction term between race and MSNA was not
a significant independent determinant of 24-h RQ, indicating
that the data are compatible with a similar effect of MSNA
on 24-h RQ regardless of race.
Discussion
Based on the known stimulatory effect of the sympathetic
nervous system (SNS) on lipid oxidation demonstrated in
pharmacological studies (4, 5, 12), the purpose of the present
study was to determine whether the RQ is related to the
activity of the SNS. Twenty-four-hour RQ was measured in
a respiratory chamber followed immediately by measurement of MSNA in 19 Caucasian and 20 Pima Indian males.
As previously demonstrated (2), 24-h RQ decreased, indicating a shift toward lipid oxidation, with increasing percent
body fat. However, multiple linear regression analysis revealed that MSNA was an independent determinant of 24-h
FIG. 1. Relation between basal MSNA and percent body fat. Squares,
Caucasians; triangles, Pima Indians. Separate regression lines are
shown for each group.
RQ, whereas percent body fat was not, suggesting that the
well established association between percent body fat and
RQ is mediated by the sympathetic nervous system. Furthermore, Pima Indians and Caucasians had a similar relationship between RQ and MSNA despite the previously reported (9) lower MSNA in Pima Indians for a given body size.
Although the association between RQ and MSNA was rather
weak, and MSNA only explained a small part of the variability in RQ, the findings support the idea that the sympathetic nervous system is involved in the regulation of body
weight via an effect on substrate oxidation. Other independent determinants of RQ in the present study were age and
energy balance during the stay in the chamber, which together with basal MSNA explained 45% of the variability in
RQ. It was not possible to test for the previously reported
effect of family membership (2) because only two subjects
were first degree relatives.
Several studies suggest that SNS activity may have an
effect on the lipid oxidation rate. Two-week oral administration of the b2-adrenergic agonist terbutaline caused an
increase in lipid oxidation, whereas administration of the
b-antagonist propranolol caused a decrease in lipid oxidation (4). Acute infusion of the nonselective b-adrenergic ag-
RESPIRATORY QUOTIENT AND SYMPATHETIC NERVOUS ACTIVITY
3979
In conclusion, MSNA is an independent determinant of
24-h RQ, although the association is weak, and MSNA only
explains a limited part of the variability in 24-h RQ. The
results support the hypothesis that an effect on lipid oxidation contributes to the demonstrated relationship between
low activity of the SNS and body weight gain.
Acknowledgments
The authors thank the individuals who volunteered for this study,
especially the members of the Gila River Indian Community, Mr. Frank
Gucciardo for performing the microneurography recordings, and Ms.
Christine Sinkey and Dr. Erling Anderson of the University of Iowa for
scoring the recordings.
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FIG. 2. Relation between 24-h RQ, adjusted for energy balance and
age, and basal MSNA. Squares, Caucasians; triangles, Pima Indians.
The regression line is for all subjects.
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Pima Indian subjects in the analysis to improve statistical
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