The thermogenic activity of brown fat is primarily driven by the sympathetic nervous system, reflected by a high density of nerve endings in the tissue (Figure 3
). Norepinephrine-induced adrenergic receptor signaling enhances expression of proteins involved in thermogenesis and stimulates intracellular lipolysis. Liberated fatty acids are directed to the mitochondria to be combusted, or may allosterically activate UCP1. This results in the uncoupling of complexes I–IV of the respiratory chain and ATP synthesis by proton leakage from the mitochondrial innermembrane space into the mitochondrial matrix, thereby generating heat instead of ATP. Longterm sympathetic outflow
towards the fat depots additionally leads to an increased mass of BAT depots and so-called ‘browning’ of WAT. Since activated BAT has a high capacity to take up and burn lipids and glucose, BAT is considered a promising target to combat obesity and associated diseases, including diabetes and cardiovascular disease.