Rewiring lipid Metabolism: The central role of CPT1 in metabolic dysfunction.

Carnitine palmitoyltransferase 1 (CPT1) serves as a critical gatekeeper in mitochondrial fatty acid oxidation and plays a central role in systemic energy homeostasis. The CPT1 family comprises three isoforms-CPT1A, CPT1B, and CPT1C-which exhibit distinct tissue distributions and regulatory features, enabling specialized metabolic functions in the liver, heart, skeletal muscle, and brain. CPT1 activity is tightly controlled through multiple mechanisms, including inhibition by malonyl-CoA, epigenetic modifications, and protein-protein interactions, all of which coordinate nutrient sensing and energy adaptation. Dysregulation of CPT1 has been implicated in the development of various metabolic disorders, including obesity, metabolic (dysfunction)-associated fatty liver disease (MAFLD), diabetic cardiomyopathy, and metabolic syndrome. This review summarizes recent advances in understanding the regulatory landscape and pathological roles of CPT1 and further discusses emerging therapeutic strategies. While CPT1-targeted interventions hold promise, challenges such as isoform specificity, off-target effects, and tissue-selective delivery must be addressed to achieve precision metabolic modulation.