Human amniotic mesenchymal stem cells-conditioned medium protects mice from high-fat diet-induced obesity.
Human amniotic mesenchymal stem cells-conditioned medium protects mice from high-fat diet-induced obesity.
复制标题
人羊膜间充质干细胞条件培养基可保护小鼠免受高脂饮食引起的肥胖
DOI：
10.1186/s13287-021-02437-z
复制
发表时间：
2021-06-26
影响因子：
7.5
通讯作者：
Xin HB
中科院分区：
文献类型：
--
作者：
Tan HL;Guan XH;Hu M;Wu J;Li RZ;Wang LF;Huang HD;Yu ZP;Wang XY;Xiao YF;Deng KY;Xin HB
肥胖是一种以脂肪过度堆积为特征的代谢紊乱综合征，与多种疾病有关。人羊膜间充质干细胞（human amniotic mesenchymal stem cells，hAMSCs）具有多能性、低免疫原性、无致瘤性、旁分泌作用和无伦理学顾虑等特点，在细胞治疗中具有巨大的潜力。最近，我们观察到hAMSC及其条件培养基（hAMSCs-CM）有效地修复皮肤损伤，抑制肝细胞癌，并减轻高脂饮食（HFD）诱导的糖尿病。然而，hAMSCs-CM对高脂饮食（HFD）诱导的肥胖的作用和潜在机制尚未探索。流式细胞术、RT-PCR和免疫荧光检测证实hAMSCs的特性。通过给予HFD 15周诱导肥胖小鼠，同时每周腹腔注射hAMSCs-CM以评价hAMSCs-CM对HFD诱导的肥胖的影响。GTT和ITT测定用于评估hAMSCs-CM对HFD诱导的葡萄糖耐量和胰岛素抵抗的影响。采用组织学染色法观察小鼠脂肪组织脂质蓄积和脂肪细胞肥大情况，并观察血脂及肝肾功能的变化。通过检查小鼠的耗氧量（VO 2）、二氧化碳产生量（VCO 2）以及食物和水摄入量来监测hAMSCs-CM在能量稳态中的作用。采用Western blot、RT-PCR和免疫荧光染色检测葡萄糖代谢、脂肪酸β氧化、产热、脂肪生成和炎症相关基因的表达。以3 T3-L1前脂肪细胞和RAW264.7细胞为实验材料，研究hAMSCs-CM在体外脂肪形成和M1/M2巨噬细胞极化中的作用。hAMSCs-CM通过抑制脂肪生成和脂肪生成、促进能量消耗和减少炎症，显著抑制HFD诱导的小鼠肥胖。hAMSCs-CM抗肥胖的机制可能与抑制PPARγ和C/EBPα介导的脂质合成和脂肪形成，促进GLUT 4介导的葡萄糖代谢，提高UCP 1/PPARα/PGC 1 α调节的能量消耗，增强STAT 3-ARG 1介导的M2型巨噬细胞极化有关。我们的研究表明，hAMSC通过其旁分泌效应显著减轻HFD诱导的肥胖。显然，我们的研究结果开辟了一个有吸引力的治疗模式，预防和治疗肥胖症和其他代谢紊乱的临床。从hAMSC分泌的细胞因子、外来体或微泡通过抑制脂质产生和脂肪形成、促进能量消耗和减少炎症来显著抑制HFD诱导的小鼠肥胖。 在线版本包含补充材料，可通过10.1186/s13287-021-02437-z获得。
Obesity is a metabolic disorder syndrome characterized by excessive fat accumulation that is related to many diseases. Human amniotic mesenchymal stem cells (hAMSCs) have a great potential for cell-based therapy due to their characteristics such as pluripotency, low immunogenicity, no tumorigenicity, potent paracrine effects, and no ethical concern. Recently, we observed that both hAMSCs and their conditioned medium (hAMSCs-CM) efficiently repaired skin injury, inhibited hepatocellular carcinoma, and alleviated high-fat diet (HFD)-induced diabetes. However, the effects and the underlying mechanisms of hAMSCs-CM on high-fat diet (HFD)-induced obesity were not explored. The characteristics of hAMSCs were confirmed by flow cytometry, RT-PCR, and immunofluorescence. Obese mice were induced by administrating HFD for 15 weeks and simultaneously, the mice were intraperitoneally injected with hAMSCs-CM weekly to evaluate the effects of hAMSCs-CM on HFD-induced obesity. GTT and ITT assays were used to assess the effects of hAMSCs-CM on HFD-induced glucose tolerance and insulin resistance. The lipid accumulation and adipocytes hypertrophy in mouse adipose tissues were determined by histological staining, in which the alterations of blood lipid, liver, and kidney function were also examined. The role of hAMSCs-CM in energy homeostasis was monitored by examining the oxygen consumption (VO2), carbon dioxide production (VCO2), and food and water intake in mice. Furthermore, the expressions of the genes related to glucose metabolism, fatty acid β oxidation, thermogenesis, adipogenesis, and inflammation were determined by western blot analysis, RT-PCR, and immunofluorescence staining. The roles of hAMSCs-CM in adipogenesis and M1/M2 macrophage polarization were investigated with 3T3-L1 preadipocytes or RAW264.7 cells in vitro. hAMSCs-CM significantly restrained HFD-induced obesity in mice by inhibiting adipogenesis and lipogenesis, promoting energy expenditure, and reducing inflammation. The underlying mechanisms of the anti-obesity of hAMSCs-CM might be involved in inhibiting PPARγ and C/EBPα-mediated lipid synthesis and adipogenesis, promoting GLUT4-mediated glucose metabolism, elevating UCP1/PPARα/PGC1α-regulated energy expenditure, and enhancing STAT3-ARG1-mediated M2-type macrophage polarization. Our studies demonstrated that hAMSCs significantly alleviated HFD-induced obesity through their paracrine effects. Obviously, our results open up an attractive therapeutic modality for the prevention and treatment of obesity and other metabolic disorders clinically. The cytokines, exosomes, or micro-vesicles secreted from hAMSCs significantly inhibited HFD-induced obesity in mice by inhibiting lipid production and adipogenesis, promoting energy consumption, and reducing inflammation. The online version contains supplementary material available at 10.1186/s13287-021-02437-z.
登录
查看更多内容
影响因子：
16.6
作者：
Lee, Hwan Hee;An, Seung Min;Kwon, Hyug Moo
通讯作者：
Kwon, Hyug Moo
影响因子：
5.6
作者：
Jung UJ;Choi MS
通讯作者：
Choi MS
人羊膜间充质干细胞抑制荷瘤小鼠的肝细胞癌
影响因子：
5.3
作者：
Liu QW;Li JY;Zhang XC;Liu Y;Liu QY;Xiao L;Zhang WJ;Wu HY;Deng KY;Xin HB
通讯作者：
Xin HB
影响因子：
29
作者：
Moreno-Aliaga, Maria J.;Perez-Echarri, Nerea;Bustos, Matilde
通讯作者：
Bustos, Matilde
影响因子：
6.5
作者：
Brocker, Chad N.;Patel, Daxesh P.;Gonzalez, Frank J.
通讯作者：
Gonzalez, Frank J.