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Inhibition of adipocyte differentiation can be used as a strategy for preventing adipose tissue expansion and, consequently, for obesity management. Since reactive oxygen species (ROS) have emerged as key modulators of adipogenesis, the effect of menadione (a synthetic form of vitamin K known to induce the increase of intracellular ROS) on 3T3-L1 preadipocyte differentiation was studied. Menadione (15 μM) increased ROS and lipid peroxidation, generating mild oxidative stress without affecting cell viability. Menadione drastically inhibited adipogenesis, accompanied by decreased intracellular lipid accumulation and diminished expression of the lipo/adipogenic markers peroxisome proliferator-activated receptor (PPAR)γ, fatty acid synthase (FAS), CCAAT/enhancer-binding protein (C/EBP) α, fatty acid binding protein (FABP) 4, and perilipin. Menadione treatment also increased lipolysis, as indicated by augmented glycerol release and reinforced by the increased expression of hormone-sensitive lipase (HSL). Additionally, menadione increased the inhibitory phosphorylation of acetyl-CoA-carboxylase (ACC), which results in the inhibition of fatty acid synthesis. As a consequence, triglyceride content was decreased. Menadione also inhibited the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Further, treatment with increased concentration of insulin, a potent physiological activator of the PI3K/Akt pathway, rescued the normal level of expression of PPARγ, the master regulator of adipogenesis, and overcame the restraining effect of menadione on the differentiation capacity of 3T3-L1 preadipocytes. Our study reveals novel antiadipogenic action for menadione, which is, at least in part, mediated by the PI3K/Akt pathway signaling and raises its potential as a therapeutic agent in the treatment or prevention of adiposity. Fil: Funk, Melania Iara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina Fil: Conde, Melisa Ailén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
