Mechanisms and therapeutic potential of AMPK signaling pathway in the regulation of lipid metabolism.

AMP-activated protein kinase (AMPK) is a central energy sensor that maintains systemic lipid homeostasis. Its therapeutic potential in metabolic diseases, including non‑alcoholic fatty liver disease, atherosclerosis, and obesity, has attracted growing interest. In this review, we systematically summarize the molecular architecture and activation mechanisms of AMPK. We also discuss its tissue‑specific regulatory networks in the liver, adipose tissue, skeletal muscle, macrophages, and the central nervous system. AMPK coordinates metabolic balance through multiple pathways. These include suppression of de novo lipogenesis, enhancement of fatty acid oxidation, modulation of cholesterol metabolism, and promotion of autophagy and lipophagy. We also review the development of AMPK-targeting agents, from natural products to synthetic agonists, and evaluate their therapeutic implications. Collectively, this review provides a conceptual framework for understanding AMPK‑mediated lipid regulation and highlights directions for future investigation.