Adiponectin up-regulates Ferritin Heavy Chain in skeletal muscle cells

Abstract

Objective. Adiponectin is an adipocyte-derived protein, which acts to reduce insulin resistance in the liver and muscle and also inhibits atherosclerosis. Although adiponectin reportedly enhances AMPK and inhibits TNFα action downstream from the adiponectin signal, the precise physiological mechanisms by which adiponectin acts on skeletal muscles remain unknown.

Research Design and Methods. We treated murine primary skeletal muscle cells with recombinant full length human adiponectin for 12 hrs and searched, using two dimensional electrophoresis, for proteins up-regulated more than 3-fold by adiponectin as compared with untreated cells.

Results. We found one protein which was increased 6.3-fold with adiponectin incubation. MALDI-TOF mass spectrometric analysis identified this protein as ferritin heavy chain (FHC). When murine primary skeletal muscle cells were treated with adiponectin, IκB-α phosphorylation was observed, suggesting that adiponectin stimulates NF-κB activity. In addition, FHC up-regulation by adiponectin was inhibited by NF-κB inhibitors. These results suggest NF-κB activation to be involved in FHC up-regulation by adiponectin. Other NF-κB target genes, MnSOD and iNOS were also increased by adiponectin treatment. We performed an ROS assay using CM-H₂DCFDA fluorescence and found that ROS-reducing effects of adiponectin were abrogated by FHC or MnSOD siRNA induction.

Conclusion. We have demonstrated that adiponectin up-regulates FHC in murine skeletal muscle tissues, suggesting that FHC elevation might partially explain how adiponectin protects against oxidative stress in skeletal muscles.