AMPKα

AMPKα is the catalytic subunit of the heterotrimeric AMP-activated protein kinase (AMPK) complex and includes AMPKα1 and AMPKα2 isoforms^[1]. Phosphorylation at Thr172 is critical for AMPK activation, linking upstream kinases including LKB1, CaMKK, and TAK1 to cellular energy signaling^[1]. Mechanistically, AMPK coordinates energy homeostasis through lipid metabolism, glucose metabolism, mitochondrial dynamics, and cell-cycle regulation^[2]. In disease models, AMPK signaling regulates hepatic steatosis through the AMPK-S6K1-LXRα axis, suppressing lipogenic gene induction and triglyceride accumulation^[3]. In cardiovascular research, activated AMPKα isoforms, particularly AMPKα2, remodel energy metabolism, improve mitochondrial dysfunction, activate mitophagy, reduce oxidative stress, and protect cardiac function in heart failure^[1]. Compared with related isoforms, AMPKα2 is the predominant catalytic isoform in the heart, whereas AMPKα1 selectively mediates effects of Compound-13/C2 and contributes strongly to lipid-synthesis inhibition in hepatocytes^[1][4]. For experimental applications, AMPK activators include indirect and direct agents, but current activators remain limited by incomplete subtype selectivity^[1][5].