Adiponectin upregulates ferritin heavy chain in skeletal muscle cells

Yuichi Ikegami, Kouichi Inukai, Kenta Imai, Yasushi Sakamoto, Hideki Katagiri, Susumu Kurihara, Takuya Awata, Shigehiro Katayama

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)


OBJECTIVE-Adiponectin is an adipocyte-derived protein that acts to reduce insulin resistance in the liver and muscle and also inhibits atherosclerosis. Although adiponectin reportedly enhances AMP-activated protein kinase and inhibits tumor necrosis factor-α 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 h and searched, using two-dimensional electrophoresis, for proteins upregulated more than threefold by adiponectin compared with untreated cells. RESULTS-We found one protein that was increased 6.3-fold with adiponectin incubation. MALDI-TOF (matrix-assisted laser desorption/ionization-top of flight) mass spectrometric analysis identified this protein as ferritin heavy chain (FHC). When murine primary skeletal muscle cells were treated with adiponec-tin, IκB-α phosphorylation was observed, suggesting that adiponectin stimulates nuclear factor (NF)-κB activity. In addition, FHC upregulation by adiponectin was inhibited by NF-κB inhibitors. These results suggest NF-κB activation to be involved in FHC upregulation by adiponectin. Other NF-κB target genes, manganese superoxide dismutase (MnSOD) and inducible nitric oxide synthase (iNOS), were also increased by adiponectin treatment. We performed a reactive oxygen species (ROS) assay using CM-H2DCFDA fluorescence and found that ROS-reducing effects of adiponectin were abrogated by FHC or MnSOD small-interfering RNA induction. CONCLUSIONS-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.

Original languageEnglish
Pages (from-to)61-70
Number of pages10
Issue number1
Publication statusPublished - 2009 Jan


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