Figure 7
Diagram showing the cAMP-SIK axis in adaptive thermogenesis of brown adipose tissue. There are no sympathetic inputs to brown adipocytes under thermoneutrality. PKA is inactive due to lower intracellular cAMP levels. Consequently, Sik2 is hypo-phosphorylated and becomes active, which leads to suppression of Ucp1 transcription. Under cold stimulation, catecholamines released from sympathetic nerves engage βARs (Adrb1–3), elevate intracellular cAMP levels and activate PKA in brown adipocytes through the activation of Gnas and adenylate cyclases. Then PKA phosphorylates and inhibits Sik2, which will promote Ucp1 transcription and ultimately adaptive thermogenesis.
