Figure 1.

cAMP-PKA signalling pathway and its signalling networks. Sympathetic neurons release NE and activate β-AR on adipocytes, thereby activating AC which catalyses cAMP, resulting in PKA phosphorylation and activation of HSL and other components of the lipolysis pathway. PKA also activates the p38 MAPK pathway, which leads to increased UCP1 transcription and the expression of other prothermogenic genes. New regulatory factors affecting thermogenesis via the cAMP-PKA pathway are also continuously being discovered, including IRE-1, APPL1, and Drp1. The cGAS-STING pathway activated by mitochondrial stress inhibits PKA signal transduction by activating PDE, thus inhibiting BAT thermogenesis. NE: norepinephrine; β-AR: β-adrenergic receptor; AC: adenylyl cyclase; cAMP: cyclic adenosine monophosphate; PKA: protein kinase A; HSL: hormone-sensitive triglyceride lipase; p38 MAPK: p38 mitogen-activated protein kinase; UCP1: uncoupling protein 1; IRE-1: inositol-requiring enzyme-1α; APPL1: adaptor protein containing the pleckstrin homology domain, phosphotyrosine binding domain and leucine zipper motif; Drp1: dynamin-related protein 1; cGAS: cGMP-AMP (cGAMP) synthase; STING: stimulator of interferon genes; PDE: phosphodiesterase; BAT: brown adipose tissue