Rhodiola‐induced inhibition of adipogenesis involves dysfunctional antioxidant response associated with proline‐linked pentose phosphate pathway

Abstract

Recent research suggests that increased reactive oxygen species production from accumulated fat in obesity leads to elevated systemic oxidative stress, contributing to the development of obesity-linked diseases. The aim of this study was to investigate dietary phenolic-linked changes of key enzymes associated with endogenous antioxidant enzyme response (AER) and energy-linked pathways during the differentiation of 3T3-L1 adipocytes based on the proline-linked pentose phosphate pathway (PLPPP) model. We hypothesized that, in differentiating preadipocytes, proline dehydrogenase (PDH) activity may increase due to requirement of energy, which also can be coupled to enhanced glucose-6-phosphate dehydrogenase (G6PDH) activity required for NADPH generation necessary for stimulation of AER. Treatment of Rhodiola extracts high in phenolics inhibited the activity of PDH and G6PDH as well as the differentiation of 3T3-L1 adipocytes. The inhibition of PDH and G6PDH by Rhodiola likely prevents proline oxidation required for critical ATP generation that is coupled to AER via PPP. This indicates that Rhodiola can disrupt proline-linked energy generation and AER via PPP, leading to suppression of adipogenesis. This provides a biochemical rationale for studies to identify the roles of phenolic phytochemicals as anti-adipogenic agents that can modulate cellular redox environment in adipocytes.