Rhodiola‐induced anti‐adipogenic effect correlates with coordinated changes of antioxidant responses in 3T3‐L1 cells

Abstract

Adipogenesis is a key process in the development of obesity and accumulated lipids of adipose tissue in obese state generate excessive reactive oxygen species (ROS), leading to elevated systemic oxidative stress. We have shown that Rhodiola extract dose‐dependently suppressed adipogenesis and ROS level in a PPARγ‐dependent manner. Here we investigated whether the anti‐adipogenic effect of Rhodiola extract and tyrosol, a major phenolic compound present in Rhodiola, alters endogenous antioxidant enzyme responses linked to hexose monophosphate (HMP) shunt during adipogenesis. 3T3‐L1 preadipocytes were differentiated with varying concentrations of Rhodiola extract or tyrosol for up to 8 days. Treatment of Rhodiola or tyrosol significantly inhibited mRNA level and enzyme activity of glucose‐6‐phosphate dehydrogenase (G6PD), a rate‐limiting enzyme in HMP pathway. These treatments also markedly reduced mRNA expression of glutathione reductase (GR) and NADPH oxidase (NOX4), a major ROS generator in adipocytes. The inhibition of G6PD likely prevented NADPH production required for NOX4 and lipid synthesis, resulting in reduced ROS level and GR activity. However, copper‐zinc superoxide dismutase and catalase mRNAs were expressed at high levels and not significantly affected. These results indicate that Rhodiola‐induced antioxidant effect is attributable to a phenolic tyrosol and may involve direct downregulation of PPARγ or via inhibition of HMP pathway linked to antioxidant responses in adipocytes.