Short-term sympathoadrenal inhibition augments the thermogenic response to β-adrenergic receptor stimulation

Abstract

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.

Regulators of Human White Adipose Browning: Evidence for Sympathetic Control and Sexual Dimorphic Responses to Sprint Interval Training

“…Clonidine is a blood pressure medication; the mechanism of action is via pre-junctional stimulation of alpha-2-adrenergic receptors. We, and others, have previously demonstrated that short-term clonidine use (2-to-7 days) results in centrally mediated peripheral sympathetic inhibition, as reflected by decreased plasma norepinephrine concentration and release, and attenuated skeletal muscle sympathetic nerve activity [21], [22].…”

“…Glucose concentration was analyzed immediately (from ∼1 ml whole blood) using an automated device (2300 STAT Plus Glucose Lactate Analyzer, YSI Inc., Yellow Springs, Ohio, USA) and insulin concentration via ELISA (ALPCO Diagnostics, Salem, NH, USA). In addition, our laboratory has an interest in the adipokine, pigment epithelium derived factor (PEDF), a physiological determinant of insulin sensitivity, oxidative stress and inflammation [19]–[21], [23]. Plasma PEDF concentration was also determined via ELISA (Millipore Corporation, Billerica, MA, USA).…”

Sympathetic responses to repetitive trans-spinal magnetic stimulation

“…Efferent multiunit postganglionic MSNA was measured from the peroneal nerve via standard microneurography procedures as previously described [2,3,21]. Neurograms were considered acceptable as recordings of efferent MSNA according to previously published criteria [22,36], and were analyzed independently by two investigators (R.J.P and C.B.)…”

“…Our laboratory has a long-standing interest in sympathetic control of metabolism and blood glucose regulation [15,20,21,28], thus we also determined the influence of rTSMS on circulating concentrations of insulin and glucose. Prior to, during the final 30 s of, and 10 min following stimulation *15 ml of venous blood was collected in chilled tubes (10 ml preserved with K 3 ethylendiaminetetraacetic acid; 5 ml preserved with ethylene glycol tetraacetic acid/glutathione) for measurement of plasma concentrations of glucose and insulin, and also catecholamines.…”

Contribution of Catecholamine Reactive Intermediates and Oxidative Stress to the Pathologic Features of Heart Diseases

“…The levels of plasmatic and/or cardiac plasmatic levels are shown to be increased in ageing [6], embryonic development [7,8] or stress [9][10][11], but also in heart failure (HF) [6,12,13], and ischemia reperfusion (I/R) injury [14,15]. Several other conditions, namely life style or hormonal status, have been associated to changes in the adrenoceptors response and catecholamine release [16][17][18]. The main cardiac actions and pathologies or syndromes where ADR and/or NA are involved will be addressed during this review.…”