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Respiratory Quotient Is Inversely Associated with Muscle Sympathetic Nerve Activity

Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85016

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: ssnitker{at}phx.niddk.nih.gov

	Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
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 ±SD, 33 ± 9 yr, 91 ± 23 kg, and 28 ± 11% body fat) and 20 Pima Indians (30 ± 5 yr, 94 ± 25 kg, and 35 ± 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 = -0.41; P = 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.

	Introduction

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OBESITY 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

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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 the Gila River Indian Community. All subjects gave written informed consent.

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

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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 = 0.47, P = 0.04 in Caucasians; r = 0.70, P = 0.006 in Pima Indians), but independent of percent body fat, basal MSNA was, on the average, 8 ± 5 bursts/min lower (mean ± SD; P = 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 = 0.01), energy balance (P = 0.002), and age (P = 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 = -0.41; P = 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 = 0.03), but not in Pima Indians (P = 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.

View larger version (16K): [in this window] [in a new window]   Figure 1. Relation between basal MSNA and percent body fat. Squares, Caucasians; triangles, Pima Indians. Separate regression lines are shown for each group.

View larger version (16K): [in this window] [in a new window]   Figure 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.

	Discussion

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Several studies suggest that SNS activity may have an effect on the lipid oxidation rate. Two-week oral administration of the ß₂-adrenergic agonist terbutaline caused an increase in lipid oxidation, whereas administration of the ß-antagonist propranolol caused a decrease in lipid oxidation (4). Acute infusion of the nonselective ß-adrenergic agonist isoproterenol caused a decrease in forearm RQ in lean men (12). Similarly, infusion of norepinephrine caused a decrease in whole body RQ (5). The physiological background for these findings is not known, but contributing mechanisms are suggested by the stimulatory effect of norepinephrine on lipolysis (5) and the stimulatory effect of isoproterenol on nonesterified fatty acid uptake in muscle (12). The evidence of a stimulatory effect of the SNS on lipid oxidation and the relationship between low lipid oxidation and weight gain combine to suggest that low lipid oxidation may contribute to the higher rates of weight gain in individuals with low SNS activity (6).

The mechanism responsible for the previously established (9) increase in MSNA with increasing percent body fat is not known. Leptin is a possible candidate, because it is secreted in proportion to percent body fat (13, 14) and dramatically stimulates SNS outflow in animals (15, 16).

The association between 24-h RQ and MSNA was statistically significant only in Caucasians. The weaker association in Pima Indians may be due to differences in body composition between the two groups, as suggested by the absence of an increase in fat oxidation in obese individuals in response to isoproterenol (12). As a multiple linear regression analysis indicated that the data are compatible with a similar effect of MSNA on RQ regardless of race, the inclusion of the Pima Indian subjects in the analysis to improve statistical power is justified.

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.

Received April 16, 1998.

Revised July 30, 1998.

Accepted August 6, 1998.

	References

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