Urinary Norepinephrine Is a Metabolic Determinant of 24-Hour Energy Expenditure and Sleeping Metabolic Rate in Adult Humans

Abstract

Background: Interindividual variability in 24-hour energy expenditure (24EE) during energy-balance conditions is mainly determined by differences in body composition and demographic factors. Previous studies suggested that 24EE might also be influenced by sympathetic nervous system activity via catecholamine (norepinephrine, epinephrine) secretion. Therefore, we analyzed the association between catecholamines and energy expenditure in 202 individuals from a heterogeneous population of mixed ethnicities.

Methods: Participants (n = 202, 33% female, 14% black, 32% white, 41% Native American, 11% Hispanic, age: 36.9 ± 10.3 y [mean ± SD], percentage body fat: 30.3 ± 9.4) resided in a whole-room calorimeter over 24 hours during carefully controlled energy-balance conditions to measure 24EE and its components: sleeping metabolic rate (SMR), awake-fed thermogenesis (AFT), and spontaneous physical activity (SPA). Urine samples were collected, and 24-h urinary epinephrine and norepinephrine excretion rates were assessed by high-performance liquid chromatography.

Results: Both catecholamines were associated with 24EE and SMR (norepinephrine: +27 and +19 kcal/d per 10 μg/24h; epinephrine: +18 and +10 kcal/d per 1 μg/24h) in separate analyses after adjustment for age, sex, ethnicity, fat mass, fat-free mass, calorimeter room, temperature, and physical activity. In a multivariate model including both norepinephrine and epinephrine, only norepinephrine was independently associated with both 24EE and SMR (both P < .008), whereas epinephrine became insignificant. Neither epinephrine nor norepinephrine were associated with adjusted AFT (both P = .37) but epinephrine was associated with adjusted SPA (+0.5% per 1 μg/24h).

Conclusions: Our data provide compelling evidence that sympathetic nervous system activity, mediated via norepinephrine, is a determinant of human energy expenditure during nonstressed, eucaloric conditions.

Trial registration: ClinicalTrials.gov NCT00856609 NCT00523627 NCT00687115 NCT00342732.

Keywords: catecholamines; energy expenditure; epinephrine; norepinephrine; obesity; sympathetic nervous system.

Published by Oxford University Press on behalf of the Endocrine Society 2020.

Figures

Figure 1.

Associations between adiposity measures and 24-hour urinary norepinephrine and epinephrine excretion rates during isocaloric conditions. Association between urinary norepinephrine excretion and (A), body mass index (BMI) and (B), percentage body fat by dual-energy X-ray absorptiometry (DXA). Association between urinary epinephrine excretion and (C), BMI and (D), percentage body fat by DXA. Black circles denote male, white circles denote female participants. Y-axes are formatted on a logarithmic scale (log10) to account for the skewed data distribution of raw catecholamine values.

Figure 2.

Greater 24-hour urinary (A), norepinephrine and (B), epinephrine excretion rates were associated with relatively higher adjusted 24-hour energy expenditure (24EE) during energy balance and weight stability. On average (A), a greater urinary norepinephrine excretion rate by 10 μg/24h and (B), a greater urinary epinephrine excretion rate by 1 μg/24h were associated with a greater adjusted 24EE by 27 kcal/d (CI: 13 -40 kcal/d) and 18 kcal/day (CI: 7-30 kcal/d), respectively. The adjusted 24EE values were calculated via linear regression analysis including fat-free mass, fat mass, age, sex, ethnicity, calorimeter temperature, spontaneous physical activity, and calorimeter room as covariates after adding the average 24EE to the residual values obtained from the regression model. X-axes are formatted on a logarithmic scale (log10) to account for the skewed data distribution of raw catecholamine values. Black circles denote male, white circles denote female participants.

Figure 3.

Associations between 24-hour urinary norepinephrine and epinephrine excretion rates and components of 24-hour energy expenditure (24EE) during energy balance. Associations between urinary (A), norepinephrine and (B), epinephrine excretion rates and adjusted sleeping metabolic rate (SMR). On average, a greater urinary norepinephrine excretion rate by 10 μg/24h and a greater urinary epinephrine excretion rate by 1 μg/24h were associated with a greater adjusted SMR by 19 kcal/d (CI: 9-29 kcal/d) and 10 kcal/day (CI: 2-19 kcal/d), respectively. Associations between urinary (C), norepinephrine and (D), epinephrine excretion rates and adjusted energy expenditure in the inactive, awake state (EE0). On average, a greater urinary norepinephrine excretion rate by 10 μg/24h and a greater urinary epinephrine excretion rate by 1 μg/24h were associated with a greater adjusted EE0 by 18 kcal/d (CI: 8-27 kcal/d) and 11 kcal/d (CI: 3-20 kcal/day), respectively. Lack of associations between urinary (E), norepinephrine and (F), epinephrine excretion rates and adjusted awake-fed thermogenesis (AFT). All adjusted EE measures (SMR, EE0, and AFT) were calculated via linear regression analysis including fat-free mass (FFM), fat mass (FM), age, sex, ethnicity, calorimeter temperature, and calorimeter room as covariates after adding the respective average value calculated in the whole cohort to the residual values obtained from the respective regression model. X-axes are formatted on a logarithmic scale (log10) to account for the skewed data distribution of raw catecholamine values. Black circles denote male, white circles denote female participants.