P 054 - Mitochondrial dynamics impairment leads to adipogenesis failure

Abstract

The white adipose tissue (WAT) is crucial for maintaining metabolism homeostasis by storing lipids and/or by secreting adipokines. A healthy WAT relies on continuous renewal, through a multi-step process called adipogenesis. Upon failure, the risk for lipotoxicity across the organism is higher and insulin resistance can arise in several tissues. A likely contributor for adipogenesis failure is mitochondrial dysfunction and subsequently cellular redox changes. Using 3T3-L1 cells, we have found that exposing them to hyperoxia (as a source of oxidative stress) for 8 days led to adipogenesis impairment, confirmed by oil red staining and transcription factors qPCRs. In our model, oxidative stressed preadipocytes exhibited mitochondrial dynamics diminishment (live cell imaging), Reactive Oxygen Species (ROS) production (fluorescence probe), less mitochondrial mass (WB and qPCR), smaller ATP/ADP ratio (HPLC) and less respiration capacity (Seahorse). In fact, challenging cells with antimycin, under normoxic conditions, showed similar features to hyperoxic treated cells in what adipogenesis is concerned. Recently, we found NFkB to be activated during the 8 days of hyperoxia in contrast to NFkB levels of differentiating cells which decreased after 2 days. We are convinced that mitochondrial dysfunction during aging/oxidative stress activates NFkB, blocking the main transcription factors and impairing adipogenesis.