Figure 2.

Illustration of the general mechanism of brown adipose tissue (BAT) activation and recruitment, as well as the other molecular mechanisms involved. Briefly, cold exposure, exercise, natural/pharmacological products, and other stimuli can activate sympathetic neurons innervating BAT release norepinephrine (NE), which binds to β3-adrenergic receptors (β3-AR) converting ATP to cyclic adenosine monophosphate (cAMP). Subsequently, cAMP activates protein kinase A (PKA), which then activate hormone-sensitive lipase (HSL) to liberate fatty acids (FAs) from triacylglyceride (TAG) stores through lipolysis, which in turn upregulate uncoupling protein 1 (UCP1) located in the mitochondria. Subsequently, the uptake of circulating free fatty acids (FFAs) and glucose contributes to the regeneration of intracellular triglyceride stores. Glucose is transported into the cell by glucose transporters (GLUTs), while FFAs are transported via cluster of differentiation 36 (CD36). On the other hand, activation of AM-activated protein kinase (AMPK) induces the complex of adipogenic and thermogenic transcriptional factors such as NAD-dependent deacetylase sirtuin-1 (SIRT1), proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), and transcriptional factor PR domain containing 16 (PRDM16), which in turn increase UCP-1-driven thermogenesis and energy expenditure.