School of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain.
Instituto de Investigación Sanitaria Pere Virgili, University Hospital of Tarragona Joan XXIII, 43007 Tarragona, Spain.
Int J Mol Sci. 2022 Dec 10;23(24):15682. doi: 10.3390/ijms232415682.
Understanding the signaling cascades that govern adipocyte metabolism and differentiation is necessary for the development of therapies for obesity. Toll-like receptors (TLRs) are key mediators in adipogenesis, but their specific role is not completely understood. In this study, siRNA knockdown of in 3T3-L1 cells allowed them to differentiate more efficiently into adipocytes, whereas the opposite was observed for the knockdown of . At the same time, we show that TLR2 knock-out mice spontaneously developed mature-onset obesity and insulin resistance. Besides a higher incidence of hyperplasia and hypertrophy in white adipose tissue (WAT), we found a significantly increased number of adipocyte precursor cells in TLR2 mice compared to TLR4 mice. Interestingly, genetic inactivation of in TLR2 mice reverted their increased adiposity, insulin resistance, and restored normal levels of adipocyte precursor cells. These findings provide evidence that TLR2 and TLR4 play opposing roles in WAT homeostasis and point to the existence of cross-regulation among TLR2 and TLR4 during adipocyte differentiation both in vitro and in vivo.
了解调节脂肪细胞代谢和分化的信号级联对于肥胖症治疗方法的开发是必要的。 Toll 样受体 (TLR) 是脂肪生成的关键介质，但它们的具体作用尚不完全清楚。在这项研究中，siRNA 敲低 3T3-L1 细胞中的 使其更有效地分化为脂肪细胞，而敲低 的则相反。同时，我们表明 TLR2 敲除小鼠自发发展为成年期肥胖和胰岛素抵抗。除了白色脂肪组织 (WAT) 中增生和肥大的发生率更高外，我们还发现 TLR2 小鼠中的脂肪细胞前体细胞数量明显增加与 TLR4 小鼠相比。有趣的是，TLR2 小鼠中 的遗传失活使其肥胖增加、胰岛素抵抗恢复正常，并恢复了脂肪细胞前体细胞的正常水平。这些发现为 TLR2 和 TLR4 在 WAT 动态平衡中发挥相反作用提供了证据，并表明 TLR2 和 TLR4 之间存在交叉调节，无论是在体外还是在体内的脂肪细胞分化过程中。
