Figure 6.

Physiological cascade associated with human non-shivering thermogenesis (NST). NST in humans is activated by a complex physiological cascade. Cold stimuli activate gene expression of PGC-1alpha (Peroxisome proliferator-activated receptor-gamma coactivator-1alpha), NRF-1 (Nuclear respiratory factor 1), and mtTFA (Mitochondrial transcription factor A), which in turn promote mitochondrial replication. Due to this process, mitochondrial density increases and NST is enhanced. Cold stimuli also enhance β₂-AR (beta-2 adrenergic receptor) and β₃-AR (beta-3 adrenergic receptor) via the sympathetic nervous system activating the expression of UCP1, UCP2, and UCP3. This increase in UCP also enhances thermogenesis. These flows interact with one other, and each associated gene possesses SNPs that affect physiological function.