The thermic effect of feeding (TEF: increase in energy expenditure following acute energy intake) is an important physiological determinant of total daily energy expenditure and thus energy balance. Approximately 40% of TEF is believed to be mediated by sympathoadrenal activation and consequent β-adrenergic receptor stimulation of metabolism. In sedentary adults, acute administration of ascorbic acid, a potent antioxidant, augments the thermogenic response to β-adrenergic stimulation. We hypothesized that acute ascorbic acid administration augments TEF in sedentary overweight and obese adults. Energy expenditure was determined (ventilated hood technique) before and 4 h after consumption of a liquid-mixed meal (caloric equivalent 40% of resting energy expenditure (REE)) in 11 sedentary, overweight/obese adults (5 men, 6 women; age: 24 ± 2 years; BMI: 28.5 ± 1.0 kg/m 2 (mean ± s.e.)) on two separate, randomly ordered occasions: during continuous intravenous administration of saline (placebo control) and/or ascorbic acid (0.05 g/kg fat-free mass). Acute ascorbic acid administration prevented the increase in plasma concentration of oxidized low-density lipoprotein in the postprandial state (P = 0.04), but did not influence REE (1,668 ± 107 kcal/day vs. 1,684 ± 84 kcal/day; P = 0.91) or the area under the TEF response curve (33.4 ± 2.4 kcal vs. 30.5 ± 3.6 kcal; P = 0.52) (control vs. ascorbic acid, respectively). Furthermore, acute ascorbic acid administration had no effect on respiratory exchange ratio, heart rate, or arterial blood pressure in the pre-and postabsorptive states (all P > 0.64). These data imply that the attenuated TEF commonly observed with sedentary lifestyle and obesity is not modulated by ascorbic acid-sensitive oxidative stress.

Sedentary behavior is associated with an attenuated thermogenic response to b-adrenergic receptor (b-AR) stimulation, an important regulator of energy expenditure (EE) in humans. Chronic stimulation of b-ARs, via heightened activity of the sympathoadrenal system, leads to diminished b-AR function. We have investigated the hypothesis that the thermogenic response of sedentary adults to b-AR stimulation will be increased during short-term sympathoadrenal inhibition. Using a randomly ordered, repeated measures study design, resting EE (REE; indirect calorimetry, ventilated hood technique) and the % increase in EE above REE (%DEE) during acute i.v. isoproterenol administration (nonselective b-AR agonist; 6, 12, and 24 ng/kg fat-free mass per min) were determined in 16 sedentary adults (nine females and seven males, 25G1 years, body mass index: 26 . 1G0 . 9 kg/m 2 , maximal oxygen uptake: 40G2 ml/kg per min (meanGS.E.M.)) in the basal state and on the 6th day of transdermal clonidine administration (centrally acting a2-AR agonist; 0 . 2 mg/day).Relative to baseline, clonidine inhibited sympathoadrenal activity, as evidenced by decreased plasma norepinephrine concentration (1 . 04G0 . 13 vs 0 . 34G0 . 03 nmol/l; P!0 . 001), skeletal muscle sympathetic nerve activity (22 . 5G3 . 8 vs 8 . 5 G1 . 9 bursts/min; PZ0 . 003), and resting heart rate (63G2 vs 49G1 beats/min; P!0 . 001). Sympathoadrenal inhibition decreased REE (6510G243 vs 5857G218 kJ/day; P!0 . 001), increased respiratory exchange ratio (0 . 84G0 . 01 vs 0 . 86 G0 . 01; PZ0 . 03), and augmented the thermogenic response to b-AR stimulation (%DEE: 11G2, 16G2, and 24G2 vs 14G1, 20G2, and 31G2; PZ0 . 04). These data demonstrate that in sedentary humans, short-term inhibition of sympathoadrenal activity increases the thermogenic response to b-AR stimulation, an important determinant of EE and hence energy balance.

These data suggest that rTSMS does not influence SNS in adults. While rTSMS represents a novel application of TMS technology, further study and perhaps modification of the technique is required before use in clinical studies of peripheral SNS function.

Trans‐cranial magnetic stimulation (TCMS) is a non‐invasive, pain‐free technique used to stimulate and study the human brain and is able to elicit brief (< 5 s) changes in SNS activity. Use of TCMS to elicit longer‐term changes in SNS activity is problematic because magnetic stimulation of the cortex does not directly activate SNS control centers, and prolonged magnetic brain stimulation increases the risk of seizure. Repetitive trans‐spinal magnetic stimulation (rTSMS) represents a novel application of the same technology that avoids the risks associated with TCMS. We have examined the utility of rTSMS for modulation of SNS in adult humans. 32 adults (age: 18–47 yr) were randomly assigned to receive either rTSMS (1 Hz; n = 6, 10 Hz; n = 10, or 20 Hz; n = 8 at 50% intensity of stimulator output) or sham stimulation (SS; n = 8). Skeletal muscle SNS activity (MSNA; microneurography), R‐to‐R interval (RRint; ECG) and standard deviation of RRint (SDRRint; a marker of heart rate variability) were measured prior to, during, and post rTSMS or SS with the magnetic coil aligned with the spinous processes of the 6th and 7th cervical vertebrae. Compared with SS, rTSMS at any frequency did not affect any of the dependent variables: condition/time interaction ‐ MSNA: P = 0.89, RRint: P = 0.15, or SDRRint: P = 0.87. These preliminary data suggest that rTSMS does not influence SNS in adults.Support: NIA AG022053, CSU College of Applied Human Sciences