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

J Clin Endocrinol Metab. 2011 Apr;96(4):E598-605. doi: 10.1210/jc.2010-1957. Epub 2011 Jan 26.


Context: 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.

Objective: Here we studied whether blockade of β-adrenergic receptors using propranolol diminishes cold-induced thermogenesis and mitochondrial uncoupling in skeletal muscle tissue.

Design: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Controlled Clinical Trial

MeSH terms

  • Adipose Tissue, Brown / drug effects
  • Adipose Tissue, Brown / physiology*
  • Adrenergic beta-Antagonists / pharmacology*
  • Adult
  • Cold Temperature*
  • Down-Regulation / drug effects
  • Electron Transport / drug effects
  • Fatty Acids, Nonesterified / analysis
  • Fatty Acids, Nonesterified / blood
  • Humans
  • Ion Channels / metabolism
  • Male
  • Mitochondrial Proteins / metabolism
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Norepinephrine / urine
  • Propranolol / pharmacology
  • Skin Temperature / drug effects
  • Skin Temperature / physiology
  • Thermogenesis / drug effects*
  • Uncoupling Protein 3
  • Young Adult


  • Adrenergic beta-Antagonists
  • Fatty Acids, Nonesterified
  • Ion Channels
  • Mitochondrial Proteins
  • Uncoupling Protein 3
  • Propranolol
  • Norepinephrine