Beta-adrenergic receptor blockade does not inhibit cold-induced thermogenesis in humans: possible involvement of brown adipose tissue.

Abstract

Recently, brown adipose tissue (BAT) gained interest as a possible target for cold-induced thermogenesis, and therefore a target for treatment of obesity in adult humans. However, mitochondrial uncoupling takes place not only in BAT but also in skeletal muscle tissue. Both tissues may be involved in cold-induced thermogenesis, which is presumably regulated by the sympathetic nervous system. Here we studied whether blockade of β-adrenergic receptors using propranolol diminishes cold-induced thermogenesis and mitochondrial uncoupling in skeletal muscle tissue. Ten lean subjects participated in this study and stayed twice (control and β-blockade using propranolol) for 84 h in a respiration chamber-the first 36 h for baseline measurements, followed by 48 h of mild cold exposure (16 C). Energy expenditure was measured continuously. After 36 and 84 h, muscle biopsies were taken in which mitochondrial uncoupling was studied. Energy expenditure increased upon mild cold exposure (+5.0 ± 1.2 W; P < 0.005), i.e. cold-induced thermogenesis. However, contrary to our hypothesis, this cold-induced thermogenesis was not diminished after β-blockade (+4.7 ± 2.1 W for blockade vs. +5.1 ± 1.4 W for control; P = 0.59 for interaction cold blockade). Skeletal muscle mitochondrial uncoupling was significantly related to cold-induced thermogenesis in the control situation (R(2) = 0.650; P < 0.01). There was no such relation during β-blockade. Our results suggest that skeletal muscle mitochondrial uncoupling may be involved in cold-induced thermogenesis and that this may be regulated by β(2)-receptors. When the β(1)- and β(2)-receptors are blocked, a β(3)-regulated process like mitochondrial uncoupling in BAT might take over the role of skeletal muscle mitochondrial uncoupling.