Figure 3.

Mitochondrial ROS production in IR. Coenzyme Q (CoQ) synthetic pathway downregulation in IR increases H₂O₂ production from Complex II, rescued by CoQ supplementation or mitochondria-targeting catalase (mtCAT) expression. Adipocyte hypertrophy attenuates adiponectin signaling and the ceramidase activity of the adiponectin receptor, resulting in ceramide accumulation and mitochondrial dysfunction. mtROS production in the skeletal muscle is increased by excess fatty acid oxidation, either directly or indirectly, via ceramide accumulation and CoQ depletion. H₂O₂ production by mitochondria-targeting paraquat (MitoParaquat) can mimic muscle IR, reversed by mtCAT or TFAM expression. Mitochondrial dysfunction, rather than AKT inhibition by ceramide, affects GLUT4 translocation to the plasma membrane and inhibits glucose uptake.