Rosiglitazone Enhances Browning Adipocytes in Association with MAPK and PI3-K Pathways During the Differentiation of Telomerase-Transformed Mesenchymal Stromal Cells into Adipocytes
Rosiglitazone Enhances Browning Adipocytes in Association with MAPK and PI3-K Pathways During the Differentiation of Telomerase-Transformed Mesenchymal Stromal Cells into Adipocytes
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DOI：
10.3390/ijms20071618
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发表时间：
2019-04-01
影响因子：
5.6
通讯作者：
Khattak, Muhammad Nasir Khan
中科院分区：
文献类型：
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作者：
Fayyad, Abeer Maher;Khan, Amir Ali;Khattak, Muhammad Nasir Khan
肥胖是患糖尿病的主要危险因素。棕色脂肪组织（BAT）介导热量的产生，而白色脂肪组织（WAT）的功能是储存脂肪。BAT在治疗肥胖和相关疾病中的作用值得进一步研究。过氧化物酶体增殖物激活受体γ (ppar - γ)是BAT和WAT脂肪形成的主要调节因子，并在葡萄糖和脂肪酸代谢中发挥作用。脂肪组织是ppar - γ的主要表达部位。在本研究中，研究了罗格列酮对端粒酶转化间充质基质细胞（iMSCs）体外成脂分化过程中棕色脂肪形成的影响以及MAPK和PI3K通路的关联。我们的数据表明，2 μ M罗格列酮通过过表达ppar - γ和C/ ebp - α来促进脂肪形成。更具体地说，EBF2和UCP-1的上调促进了棕色脂肪的形成，分化的脂肪细胞的多室脂肪滴形态证明了这一点。我们还发现罗格列酮在分化成熟阶段显著激活MAPK和PI3K通路。总体而言，结果表明罗格列酮诱导ppar - γ过表达，进而促进脂肪形成，特别是褐变脂肪形成。本研究报道了罗格列酮在iMSCs向脂肪细胞分化过程中的褐变效应，该效应与MAPK和PI3K信号通路的激活有关。
Obesity is a major risk for diabetes. Brown adipose tissue (BAT) mediates production of heat while white adipose tissue (WAT) function in the storage of fat. Roles of BAT in the treatment of obesity and related disorders warrants more investigation. Peroxisome proliferator activator receptor gamma (PPAR-gamma) is the master regulator of both BAT and WAT adipogenesis and has roles in glucose and fatty acid metabolism. Adipose tissue is the major expression site for PPAR-gamma. In this study, the effects of rosiglitazone on the brown adipogenesis and the association of MAPK and PI3K pathways was investigated during the in vitro adipogenic differentiation of telomerase transformed mesenchymal stromal cells (iMSCs). Our data indicate that 2 mu M rosiglitazone enhanced adipogenesis by over-expression of PPAR-gamma and C/EBP-alpha. More specifically, brown adipogenesis was enhanced by the upregulation of EBF2 and UCP-1 and evidenced by multilocular fatty droplets morphology of the differentiated adipocytes. We also found that rosiglitazone significantly activated MAPK and PI3K pathways at the maturation stage of differentiation. Overall, the results indicate that rosiglitazone induced overexpression of PPAR-gamma that in turn enhanced adipogenesis, particularly browning adipogenesis. This study reports the browning effects of rosiglitazone during the differentiation of iMSCs into adipocytes in association with the activation of MAPK and PI3K signaling pathways.