Ferroptotic signaling in adipocytes mitigates obesity
The role iron dependent cell death, ferroptosis, in adipose tissue function and activity is unclear.
The researchers show that a ferroptosis signature is compromised in adipose tissues of humans and mice with obesity.
They found that activation of ferroptotic signaling by a non-lethal dose of ferroptosis agonists significantly reduces lipid accumulation in primary adipocytes and high-fat diet (HFD)-fed mice.
By constraining HIF1a availability, ferroptotic signaling in adipocytes reduces lipid accumulation and increases thermogenesis via a c-Myc-Pgc1b axis, The authors show that 5,15-dihydroxyeicosatetraenoic acid (5,15-DiHETE) activates ferroptotic signaling, resulting in the degradation of hypoxia-inducible factor-1α (HIF1α), thereby derepressing a thermogenic program regulated by the c-Myc-peroxisome proliferator-activated receptor gamma coactivator-1 beta (Pgc1β) pathway.
Thus, targeting this pathway may prevent or treat obesity and metabolic disorders.
https://www.cell.com/cell-metabolism/fulltext/S1550-4131(24)00456-X
https://sciencemission.com/ferroptotic-signaling-mitigates-obesity
