Isabel Espadas, María Ángeles Cáliz-Molina, Raúl López-Fernández-Sobrino, Concepción Panadero-Morón, Alejandro Sola-García, Mario Soriano-Navarro, Enrique Martínez-Force, Mónica Venegas-Calerón, Joaquin J Salas, Franz Martín, Benoit R Gauthier, Clara Alfaro-Cervelló, David Martí-Aguado, Vivian Capilla-González, Alejandro Martín-Montalvo
ATP citrate lyase (ACLY) inhibitors have the potential of modulating central processes in protein, carbohydrate, and lipid metabolism, which can have relevant physiological consequences in aging and age-related diseases. Here, we show that hepatic phospho-active ACLY correlates with overweight and Model for End-stage Liver Disease score in humans. Wild-type mice treated chronically with the ACLY inhibitor potassium hydroxycitrate exhibited delayed early mortality. In AML12 hepatocyte cultures, the ACLY inhibitors potassium hydroxycitrate, SB-204990, and bempedoic acid fostered lipid accumulation, which was also observed in the liver of healthy-fed mice treated with potassium hydroxycitrate...
May 17, 2024: Aging Cell