1. Knockdown of LYRM1 rescues insulin resistance and mitochondrial dysfunction induced by FCCP in 3T3-L1 adipocytes.
- Author
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Zhang M, Qin ZY, Dai YM, Wang YM, Zhu GZ, Zhao YP, Ji CB, Zhu JG, Shi CM, Qiu J, Cao XG, and Guo XR
- Subjects
- 3T3-L1 Cells, Adenosine Triphosphate biosynthesis, Animals, Glucose metabolism, Glucose Transporter Type 4 metabolism, Insulin pharmacology, Membrane Potential, Mitochondrial drug effects, Mice, Mitochondria metabolism, Phosphorylation drug effects, Protein Transport drug effects, Proton Ionophores pharmacology, Reactive Oxygen Species metabolism, Signal Transduction drug effects, Adipocytes cytology, Apoptosis Regulatory Proteins deficiency, Apoptosis Regulatory Proteins genetics, Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone pharmacology, Gene Knockdown Techniques, Insulin Resistance genetics, Mitochondria drug effects
- Abstract
LYR motif-containing 1 (LYRM1) was recently discovered to be involved in adipose tissue homeostasis and obesity-associated insulin resistance. We previously demonstrated that LYRM1 overexpression might contribute to insulin resistance and mitochondrial dysfunction. Additionally, knockdown of LYRM1 enhanced insulin sensitivity and mitochondrial function in 3T3-L1 adipocytes. We investigated whether knockdown of LYRM1 in 3T3-L1 adipocytes could rescue insulin resistance and mitochondrial dysfunction induced by the cyanide p-trifluoromethoxyphenyl-hydrazone (FCCP), a mitochondrion uncoupler, to further ascertain the mechanism by which LYRM1 is involved in obesity-associated insulin resistance. Incubation of 3T3-L1 adipocytes with 1 µM FCCP for 12 h decreased insulin-stimulated glucose uptake, reduced intracellular ATP synthesis, increased intracellular reactive oxygen species (ROS) production, impaired insulin-stimulated Glucose transporter type 4 (GLUT4) translocation, and diminished insulin-stimulated tyrosine phosphorylation of Insulin receptor substrate-1 (IRS-1) and serine phosphorylation of Protein Kinase B (Akt). Knockdown of LYRM1 restored insulin-stimulated glucose uptake, rescued intracellular ATP synthesis, reduced intracellular ROS production, restored insulin-stimulated GLUT4 translocation, and rescued insulin-stimulated tyrosine phosphorylation of IRS-1 and serine phosphorylation of Akt in FCCP-treated 3T3-L1 adipocytes. This study indicates that FCCP-induced mitochondrial dysfunction and insulin resistance are ameliorated by knockdown of LYRM1.
- Published
- 2014
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