Downregulation of lipin-1 induces insulin resistance by increasing intracellular ceramide accumulation in C2C12 myotubes
文献类型：期刊论文
| 作者 | Huang, Shujuan1,2; Huang, Suling1 ; Wang, Xi1; Zhang, Qingli3; Liu, Jia3; Leng, Ying1
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| 刊名 | INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
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| 出版日期 | 2017 |
| 卷号 | 13期号:1页码:1-12 |
| 关键词 | lipin-1 skeletal muscle insulin resistance lipid metabolism ceramide |
| ISSN号 | 1449-2288 |
| DOI | 10.7150/ijbs.17149 |
| 文献子类 | Article |
| 英文摘要 | Dysregulation of lipid metabolism in skeletal muscle is involved in the development of insulin resistance. Mutations in lipin-1, a key lipid metabolism regulator leads to significant systemic insulin resistance in fld mice. However, the function of lipin-1 on lipid metabolism and insulin sensitivity in skeletal muscle is still unclear. Herein we demonstrated that downregulation of lipin-1 in C2C12 myotubes by siRNA transfection suppressed insulin action, characterized by reduced insulin stimulated Akt phosphorylation and glucose uptake. Correspondingly, decreased lipin-1 expression was observed in palmitate-induced insulin resistance in C2C12 myotubes, suggested that lipin-1 might play a role in the etiology of insulin resistance in skeletal muscle. The insulin resistance induced by lipin-1 downregulation was related to the disturbance of lipid homeostasis. Lipin-1 silencing reduced intracellular DAG and TAG levels, but elevated ceramide accumulation in C2C12 myotubes. Moreover, the impaired insulin stimulated Akt phosphorylation and glucose uptake caused by lipin-1 silencing could be blocked by the pretreatment with SPT inhibitor myriocin, ceramide synthase inhibitor FB1, or PP2A inhibitor okadaic acid, suggested that the increased ceramide accumulation might be responsible for the development of insulin resistance induced by lipin-1 silencing in C2C12 myotubes. Meanwhile, decreased lipin-1 expression also impaired mitochondrial function in C2C12 myotubes. Therefore, our study suggests that lipin-1 plays an important role in lipid metabolism and downregulation of lipin-1 induces insulin resistance by increasing intracellular ceramide accumulation in C2C12 myotubes. These results offer a molecular insight into the role of lipin-1 in the development of insulin resistance in skeletal muscle. |
| WOS关键词 | SKELETAL-MUSCLE CELLS ; INHIBITION ; PALMITATE ; PATHWAY ; PROTEIN ; MICE ; GENE ; LIPODYSTROPHY ; METABOLISM ; SEPARATION |
| 资助项目 | National Nature Science Foundation of China[81273565] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000396426200001 |
| 出版者 | IVYSPRING INT PUBL |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/275729]  |
| 专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Leng, Ying |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Zu Chong Zhi Rd 555, Shanghai 201203, Peoples R China; 2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Zu Chong Zhi Rd 555, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Huang, Shujuan,Huang, Suling,Wang, Xi,et al. Downregulation of lipin-1 induces insulin resistance by increasing intracellular ceramide accumulation in C2C12 myotubes[J]. INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,2017,13(1):1-12. |
| APA | Huang, Shujuan,Huang, Suling,Wang, Xi,Zhang, Qingli,Liu, Jia,&Leng, Ying.(2017).Downregulation of lipin-1 induces insulin resistance by increasing intracellular ceramide accumulation in C2C12 myotubes.INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,13(1),1-12. |
| MLA | Huang, Shujuan,et al."Downregulation of lipin-1 induces insulin resistance by increasing intracellular ceramide accumulation in C2C12 myotubes".INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES 13.1(2017):1-12. |
入库方式： OAI收割
来源：上海药物研究所
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