SOD3 Is Secreted by Adipocytes and Mitigates High-Fat Diet-Induced Obesity, Inflammation, and Insulin Resistance
SOD3 Is Secreted by Adipocytes and Mitigates High-Fat Diet-Induced Obesity, Inflammation, and Insulin Resistance
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SOD3 由脂肪细胞分泌，可减轻高脂饮食引起的肥胖、炎症和胰岛素抵抗。
DOI：
10.1089/ars.2018.7628
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发表时间：
2020-01-20
影响因子：
6.6
通讯作者：
Liu, Jiankang
中科院分区：
文献类型：
--
作者：
Gao, Dan;Hu, Sijun;Liu, Jiankang
目的：研究SOD3在脂肪细胞和脂肪组织中的表达及其调控作用。结果：SOD3在成年C57BL/6J小鼠、人脂肪组织及高脂饮食（HFD）诱导肥胖小鼠的附睾脂肪组织、皮下脂肪组织和棕色脂肪组织中均有表达。研究了SOD3在原代人前脂肪细胞和小鼠骨髓间充质干细胞（BM-MSCs）分化的脂肪细胞中的表达和释放。SOD3的调控作用是通过SOD3慢病毒在人脂肪细胞和SOD3基因敲除（KO）小鼠中的敲除来确定的。SOD3在白色脂肪组织中高表达，脂肪细胞是脂肪组织中主要表达SOD3的细胞。饲喂hfd的小鼠脂肪组织中SOD3的表达显著升高。此外，与未分化的细胞相比，分化的人脂肪细胞和小鼠BM-MSCs分化的脂肪细胞中SOD3的表达和释放明显增加。此外，人类脂肪细胞中SOD3的沉默增加了参与脂质代谢途径的基因如PPAR γ和SREBP1c的表达，促进了甘油三酯的积累。最后，全球sod3 KO小鼠更肥胖，胰岛素抵抗，脂肪组织扩大，甘油三酯积累增加。创新：我们的数据表明，SOD3是由脂肪细胞分泌的，并调节脂肪组织的脂质代谢。这一重要发现可能为SOD3在肥胖及其相关代谢紊乱中的细胞保护作用开辟新的研究途径。结论：SOD3是脂肪细胞在hfd诱导肥胖时分泌的保护因子，调节脂肪组织脂质代谢。
Aims: To study the expression and regulatory role of SOD3 in adipocytes and adipose tissue. Results: SOD3 expression was determined in various tissues of adult C57BL/6J mice, human adipose tissue and epididymal adipose tissue, subcutaneous adipose tissue and brown adipose tissue of high-fat diet (HFD)-induced obese mice. SOD3 expression and release were evaluated in adipocytes differentiated from primary human preadipocytes and murine bone marrow-derived mesenchymal stem cells (BM-MSCs). The regulatory role for SOD3 was determined by SOD3 lentivirus knockdown in human adipocytes and global sod3 knockout (KO) mice. SOD3 was expressed at high levels in white adipose tissue, and adipocytes were the main cells expressing SOD3 in adipose tissue. SOD3 expression was significantly elevated in adipose tissue of HFD-fed mice. Moreover, SOD3 expression and release were markedly increased in differentiated human adipocytes and adipocytes differentiated from mouse BM-MSCs compared with undifferentiated cells. In addition, SOD3 silencing in human adipocytes increased expression of genes involved in lipid metabolic pathways such as PPAR gamma and SREBP1c and promoted the accumulation of triglycerides. Finally, global sod3 KO mice were more obese and insulin resistant with enlarged adipose tissue and increased triglyceride accumulation. Innovation: Our data showed that SOD3 is secreted from adipocytes and regulates lipid metabolism in adipose tissue. This important discovery may open up new avenues of research for the cytoprotective role of SOD3 in obesity and its associated metabolic disorders. Conclusion: SOD3 is a protective factor secreted by adipocytes in response to HFD-induced obesity and regulates adipose tissue lipid metabolism.