Urinary norepinephrine is a metabolic determinant of 24-h energy expenditure and sleeping metabolic rate in adult humans

BACKGROUND: Inter-individual 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 subjects from a heterogeneous population of mixed ethnicities. METHODS: Participants (n=202, 33% female, 14% Black, 32% Caucasian, 41% Native Americans, 11% Hispanic, age: 36.9±10.3 years (mean±SD), percentage body fat: 30.3±9.4) resided in a whole-room calorimeter over 24-h 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/day per 10 μg/24h; epinephrine: +18 and +10 kcal/day per 1 μg/24h) in separate analyses after adjustment for age, sex, ethnicity, fat mass, fat-free mass, calorimeter room and temperature, and physical activity. In a multivariable model including both norepinephrine and epinephrine, only norepinephrine was independently associated with both 24EE and SMR (both p<0.008) while epinephrine became insignificant. Neither epinephrine nor norepinephrine were associated with adjusted AFT (both p=0.37) 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 non-stressed, eucaloric conditions.