Quercetin Reduces Lipid Accumulation During Adipogenic Differentiation in Association with Stage-Dependent Mitochondrial-Redox and Metabolic Alterations Revealed by Time-Resolved 1H NMR Metabolomics.

(1) Background: Adipocyte differentiation involves coordinated changes in mitochondrial activity, redox balance, and cellular metabolism. Here, we examined how quercetin affects lipid accumulation and associated mitochondrial-redox and metabolic features during 3T3-L1 adipogenic differentiation by combining functional assays with time-resolved 1H NMR metabolomics. (2) Materials and methods: 3T3-L1 cells were differentiated for six days in the absence or presence of 20 μM quercetin. Lipid accumulation, mitochondrial membrane potential, intracellular reactive oxygen species (ROS), and intracellular metabolite profiles were assessed at defined stages of differentiation. (3) Results: Quercetin reduced lipid accumulation, mitochondrial membrane potential, and ROS accumulation, particularly at the mid-to-late stages of adipogenic differentiation. 1H NMR analysis showed lower lipid-associated resonances and changes in metabolites related to energy metabolism, choline metabolism, and amino acid metabolism in quercetin-treated cells. Orthogonal partial least squares-discriminant analysis (OPLS-DA) showed separation of the metabolic profiles of untreated and quercetin-treated cells at each measured stage. The variables contributing to this separation included lipid-associated resonances, lactate, 3-hydroxybutyrate, choline-related metabolites, and selected amino acids. (4) Conclusions: The results indicate that quercetin reduces lipid accumulation during adipogenic differentiation in association with changes in mitochondrial-redox status and intracellular metabolic profiles. Overall, the findings support stage-dependent alterations of metabolic profiles in quercetin-treated 3T3-L1 cells during adipogenic differentiation.