Describe brown adipose tissue and the mechanism of non-shivering thermogenesis.

Definition

Structure and Distinguishing Features

• Abundant in the newborn (about 5% of body weight) and in hibernating animals; largely regresses in adults, though active depots persist and can be detected on pet scanning

Mechanism — Thermogenin (ucp-1)

Cold → hypothalamus → sympathetic discharge → Noradrenaline on β3 receptors → ↑ cAMP → hormone-sensitive lipase → Free fatty acids released — both fuel and activator → Activate thermogenin (UCP-1) in the inner mitochondrial membrane → Protons bypass ATP synthase and re-enter the matrix → Gradient dissipated → energy released as heat

• Thermogenin is a physiological uncoupler — it does the same thing as 2,4-dinitrophenol, but under precise control
• Respiration runs at maximal rate with almost no ATP produced
• Thyroid hormone is permissive, inducing UCP-1 and the type II deiodinase

Physiological Importance

• The newborn cannot shiver effectively and has a large surface area to volume ratio — bat is its chief defence against cold
• Prevents neonatal hypothermia, which would otherwise cause hypoglycaemia, acidosis and increased oxygen consumption
• Arousal from hibernation in animals
• Contributes to diet-induced thermogenesis and to overall energy balance

Applied Aspects

• Preterm infants have little brown fat and are highly prone to hypothermia — the reason for warmers, skin-to-skin care and delivery-room temperature control
• Bat is being explored as a target in obesity; β3 agonists and cold exposure can activate it, but no useful drug has emerged
• Brown fat causes false positive FDG uptake on pet scans, particularly in the neck and supraclavicular region of young thin patients in cold weather — a well-recognised pitfall that may be mistaken for lymph node metastases
• Phaeochromocytoma can activate brown fat through catecholamine excess, contributing to weight loss and heat intolerance