Protein kinase A signaling pathway (PKA pathway)

The Protein Kinase A (PKA) signaling pathway in adipocytes is a fundamental biochemical cascade that regulates lipid metabolism and thermogenesis in response to hormonal stimuli (Taylor et al., 2013, Nat Rev Mol Cell Biol). Upon activation of beta-adrenergic receptors by catecholamines, adenylyl cyclase is stimulated to produce cyclic AMP (cAMP), which binds to the regulatory subunits of PKA, releasing its active catalytic subunits. In white adipose tissue, PKA phosphorylates key proteins such as perilipin-1 and hormone-sensitive lipase (HSL), initiating the hydrolysis of triglycerides into free fatty acids and glycerol for systemic energy use (Londos et al., 1999, Biochimie). In brown and beige adipocytes, the pathway induces the expression of Uncoupling Protein 1 (UCP1), which uncouples oxidative phosphorylation to generate heat (Braun et al., 2018, Front Endocrinol). Impairment of this pathway is associated with the development of obesity and insulin resistance, making its components attractive targets for metabolic disease therapies. However, therapeutic intervention is complicated by the ubiquitous nature of PKA signaling, necessitating tissue-specific or receptor-selective approaches to minimize off-target effects such as tachycardia or hypertension.

Other names

cAMP-PKA signaling pathwayBeta-adrenergic signaling in adipocytesLipolytic signaling cascade

Activation of the pathway involves GPCR-mediated cAMP production, which activates PKA to phosphorylate downstream metabolic enzymes and regulatory proteins like hormone-sensitive lipase and perilipin.