The anti‐adipogenic effect of quercetin is associated with coordinated changes of antioxidant responses during adipogenic differentiation of 3T3‐L1 cells.

Abstract

Increased reactive oxygen species (ROS) from accumulated fat in obesity has been shown to elevate systemic oxidative stress, contributing to diabetes, hypertension, and coronary heart disease. Here, we investigated the effects of a flavonoid quercetin on the changes of gene expression associated with cellular antioxidant responses and adipogenesis during differentiation of 3T3‐L1 preadipocytes. The changes in levels of lipid, ROS, mRNA expression of PPARγ, glucose‐6‐phosphate dehydrogenase (G6PDH), glutathione reductase (GR), and catalase was determined. ROS production significantly increased in parallel with lipid accumulation in adipocytes, which correlated with increased mRNA expression of all of the genes. Exposure to 100µM quercetin inhibited PPARγ (~3‐fold) and G6PDH mRNAs (~4‐fold) as well as adipogenesis and ROS accumulation compared to control. Quercetin also markedly inhibited mRNA expression of GR and catalase (~5 and 3‐fold, respectively). The inhibition of PPARγ and G6PDH by quercetin likely prevented hexose monophosphate (HMP) pathway‐mediated NADPH generation required for lipid synthesis and GR activity. These observations suggest that, during adipogenesis, the antioxidant enzymes are positively regulated to manage oxidative stress from accumulating fat, and that the anti‐adipogenic action of quercetin may involve coordinated changes of cellular redox state in adipocytes