Synthesis of cytochrome c oxidase 1 (SCO1) inhibits insulin sensitivity by decreasing copper levels in adipocytes

Biochem Biophys Res Commun. 2017 Sep 23;491(3):814-820. doi: 10.1016/j.bbrc.2017.06.124. Epub 2017 Jun 21.


Dysregulation of insulin signaling leads to type 2 diabetes mellitus (T2DM) and other metabolic disorders. Obesity is an important contributor to insulin resistance, and although the understanding of this relationship has improved in recent years, the mechanism of obesity-induced insulin resistance is not completely understood. Disorders of copper metabolism tend to accompany the development of obesity, which increases the risk of insulin resistance. Synthesis of cytochrome c oxidase 1 (SCO1) functions in the assembly of cytochrome c oxidase (COX) and cellular copper homeostasis. However, the role of SCO1 in the regulation of metabolism remains unknown. Here, we found that obese mice had higher expression of SCO1 and lower levels of copper in white adipose tissue (WAT) than did the control mice. Overexpression of SCO1 in adipocytes was associated with copper deficiency. Copper increased insulin sensitivity by decreasing the level of phosphatase and tensin homolog (PTEN) protein. Ectopic expression of SCO1 led to insulin resistance and was accompanied by a decrease in intracellular copper level, and addition of copper abolished the inhibitory effect of SCO1 on insulin sensitivity. Our results demonstrated a novel role of SCO1 in modulating insulin sensitivity via the regulation of copper concentration in WAT and suggested a potential therapeutic target for T2DM.

Keywords: Copper deficiency; Insulin sensitivity; Obesity; PTEN; SCO1.

MeSH terms

  • Adipocytes / metabolism*
  • Adipocytes / pathology
  • Adipose Tissue, White / metabolism*
  • Adipose Tissue, White / pathology
  • Animals
  • Cells, Cultured
  • Copper / metabolism*
  • Down-Regulation
  • Electron Transport Complex IV / biosynthesis*
  • Insulin / metabolism*
  • Insulin Resistance*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Chaperones
  • Obesity / metabolism*
  • Obesity / pathology


  • Insulin
  • Molecular Chaperones
  • SCO1 protein, mouse
  • Copper
  • Electron Transport Complex IV