PMID- 28647369 OWN - NLM STAT- MEDLINE DCOM- 20170912 LR - 20201209 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 491 IP - 3 DP - 2017 Sep 23 TI - Synthesis of cytochrome c oxidase 1 (SCO1) inhibits insulin sensitivity by decreasing copper levels in adipocytes. PG - 814-820 LID - S0006-291X(17)31257-3 [pii] LID - 10.1016/j.bbrc.2017.06.124 [doi] AB - 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. CI - Copyright (c) 2017. Published by Elsevier Inc. FAU - Wei, Xiang-Bo AU - Wei XB AD - Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, China. FAU - Guo, Liang AU - Guo L AD - Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, China. FAU - Liu, Yang AU - Liu Y AD - Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, China. FAU - Zhou, Shui-Rong AU - Zhou SR AD - Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, China. FAU - Liu, Yuan AU - Liu Y AD - Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, China; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China. FAU - Dou, Xin AU - Dou X AD - Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, China. FAU - Du, Shao-Yue AU - Du SY AD - Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, China. FAU - Ding, Meng AU - Ding M AD - Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, China. FAU - Peng, Wan-Qiu AU - Peng WQ AD - Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, China. FAU - Qian, Shu-Wen AU - Qian SW AD - Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, China. FAU - Huang, Hai-Yan AU - Huang HY AD - Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, China. FAU - Tang, Qi-Qun AU - Tang QQ AD - Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, China; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China. Electronic address: qqtang@shmu.edu.cn.m. LA - eng PT - Journal Article DEP - 20170621 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Insulin) RN - 0 (Molecular Chaperones) RN - 0 (SCO1 protein, mouse) RN - 789U1901C5 (Copper) RN - EC 1.9.3.1 (Electron Transport Complex IV) SB - IM MH - Adipocytes/*metabolism/pathology MH - Adipose Tissue, White/*metabolism/pathology MH - Animals MH - Cells, Cultured MH - Copper/*metabolism MH - Down-Regulation MH - Electron Transport Complex IV/*biosynthesis MH - Insulin/*metabolism MH - *Insulin Resistance MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Molecular Chaperones MH - Obesity/*metabolism/pathology OTO - NOTNLM OT - Copper deficiency OT - Insulin sensitivity OT - Obesity OT - PTEN OT - SCO1 EDAT- 2017/06/26 06:00 MHDA- 2017/09/13 06:00 CRDT- 2017/06/26 06:00 PHST- 2017/06/17 00:00 [received] PHST- 2017/06/20 00:00 [accepted] PHST- 2017/06/26 06:00 [pubmed] PHST- 2017/09/13 06:00 [medline] PHST- 2017/06/26 06:00 [entrez] AID - S0006-291X(17)31257-3 [pii] AID - 10.1016/j.bbrc.2017.06.124 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2017 Sep 23;491(3):814-820. doi: 10.1016/j.bbrc.2017.06.124. Epub 2017 Jun 21.