Knockdown of NYGGF4 (PID1) rescues insulin resistance and mitochondrial dysfunction induced by FCCP in 3T3-L1 adipocytes |
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| Authors: | Chun-Mei Shi Yu-Mei Wang Chun-Mei Zhang Jie Qiu Ya-Hui Shen Jin-Gai Zhu Lin Chen Guang-Feng Xu Ya-Ping Zhao Chen-Bo Ji Xi-Rong Guo |
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| Institution: | 1. Department of Pediatrics, Nanjing Maternity and Child Health Hospital of Nanjing Medical University, Nanjing 210004, China;2. Institute of Pediatrics of Nanjing Medical University, Nanjing 210029, China;3. Department of Child Health, Huai''an Maternity and Child Health Hospital, Huai''an 223002, China;4. The 82th Hospital of the People''s Liberation Army, Huai''an 223001, China;3. Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia;4. Diabetes and Obesity Research Program, The Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, Sydney, New South Wales 2010, Australia;5. Genentech, Inc., South San Francisco, California 94080;6. School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales 2050, Australia;1. Department of Hepatobiliary Surgery, Linyi People''s Hospital, Linyi, Shangdong, China;2. Research Center, Linyi People''s Hospital, Linyi, Shangdong, China;3. Liver Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China;4. Department of Surgery, Linyi People''s Hospital, Linyi, Shangdong, China;1. Department of Pediatric Allergy and Clinical Immunology, Trakya University, School of Medicine, Edirne, Turkey;2. Department of Internal Medicine, Trakya University, School of Medicine, Edirne, Turkey;3. Department of Biostatistics, Trakya University, School of Medicine, Edirne, Turkey;1. Department of Psychiatry, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan;2. Department of Neuropsychiatry, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan;3. Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan;4. Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan |
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| Abstract: | NYGGF4 is a recently identified gene that is involved in obesity-associated insulin resistance. Previous data from this laboratory have demonstrated that NYGGF4 overexpression might contribute to the development of insulin resistance (IR) and to mitochondrial dysfunction. Additionally, NYGGF4 knockdown enhanced insulin sensitivity and mitochondrial function in 3T3-L1 adipocytes. We designed this study to determine whether silencing of NYGGF4 in 3T3-L1 adipocytes could rescue the effect of insulin sensitivity and mitochondrial function induced by the cyanide p-trifluoromethoxyphenyl-hydrazone (FCCP), a mitochondrion uncoupler, to ascertain further the mechanism of NYGGF4 involvement in obesity-associated insulin resistance. We found that 3T3-L1 adipocytes, incubated with 5 μM FCCP for 12 h, had decreased levels of insulin-stimulated glucose uptake and had impaired insulin-stimulated GLUT4 translocation. Silencing also diminished insulin-stimulated tyrosinephosphorylation of IRS-1 and serine phosphorylation of Akt. This phenomenon contrasts with the effect of NYGGF4 knockdown on insulin sensitivity and describes the regulatory function of NYGGF4 in adipocytes insulin sensitivity. We next analyzed the mitochondrial function in NYGGF4-silenced adipocytes incubated with FCCP. NYGGF4 knockdown partly rescued the dissipation of mitochondrial mass, mitochondrial DNA, intracellular ATP synthesis, and intracellular reactive oxygen species (ROS) production occurred following the addition of FCCP, as well as inhibition of mitochondrial transmembrane potential (ΔΨm) in 3T3-L1 adipocytes incubated with FCCP. Collectively, our results suggested that addition of silencing NYGGF4 partly rescued the effect of insulin resistance and mitochondrial dysfunction in NYGGF4 silenced 3T3-L1 adipocytes incubated with FCCP, which might explain the involvement of NYGGF4-induced IR and the development of NYGGF4 in mitochondrial function. |
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