Our previous data indicate that both insulin and IGF-1 signallings dysfunction promotes the dedifferentiation of primary human and mouse white adipocytes. Based on the fact that insulin activates mTOR and inhibits autophagy, and autophagy deficiency can inhibit the differentiation of white adipocytes, we speculate that autophagy may be related to the dedifferentiation of white adipocytes. We investigated the underlying mechanism of autophagy during dedifferentiation of mouse 3T3-L1 adipocytes. After incomplete inhibition of insulin and IGF-1 signallings, 3T3-L1 adipocytes manifest dedifferentiation accompanied with an increase of autophagy level. If induction only of autophagy in the adipocytes, then the cells also occur somewhat dedifferentiation, and with a slight decrease of insulin signal, while its degree was weaker than insulin signal inhibited cells. Notably, after inhibition of the insulin and IGF-1 signallings and simultaneously inducing autophagy, the dedifferentiation of 3T3-L1 adipocytes was the most obvious compared with other groups, and the insulin and IGF-1 signallings decreases was greater than the cells with inhibition only of insulin signalling. If inhibition of both insulin signal and autophagy simultaneously, the dedifferentiation of the adipocytes reveals similar tendencies to the cells that insulin signal was inhibited. No significant dedifferentiation occurs of 3T3-L1 cells if only inhibition of autophagy. Taken all together, in this study, we proved that autophagy is positively related to the dedifferentiation of 3T3-L1 adipocytes and is regulated through the insulin-PI3K-AKT-mTOCR1-autophagy pathway. Autophagy may also has a certain degree of negative feedback affect on the insulin signalling of 3T3-L1 cells. Our work may help to better understand the biological properties of mature adipocytes and may help formulate anti-obesity strategies by regulating insulin and insulin signaling level.

我们之前的数据表明，胰岛素和 IGF-1 信号传导功能障碍都促进了原代人和小鼠白色脂肪细胞的去分化。基于胰岛素激活mTOR并抑制自噬，而自噬缺乏可抑制白色脂肪细胞的分化，我们推测自噬可能与白色脂肪细胞的去分化有关。我们研究了小鼠 3T3-L1 脂肪细胞去分化过程中自噬的潜在机制。在胰岛素和 IGF-1 信号通路受到不完全抑制后，3T3-L1 脂肪细胞表现出去分化并伴有自噬水平的增加。如果仅在脂肪细胞中诱导自噬，那么细胞也会发生一定程度的去分化，并且胰岛素信号略有下降，而其程度弱于胰岛素信号抑制细胞。值得注意的是，在抑制胰岛素和IGF-1信号同时诱导自噬后，与其他组相比，3T3-L1脂肪细胞的去分化最为明显，并且胰岛素和IGF-1信号的下降幅度大于仅抑制的细胞。的胰岛素信号。如果同时抑制胰岛素信号和自噬，则脂肪细胞的去分化显示出与胰岛素信号被抑制的细胞相似的趋势。如果仅抑制自噬，3T3-L1细胞不会发生明显的去分化。综上所述，在本研究中，我们证明自噬与 3T3-L1 脂肪细胞的去分化呈正相关，并通过胰岛素-PI3K-AKT-mTOCR1-自噬途径进行调节。自噬也可能对3T3-L1细胞的胰岛素信号产生一定程度的负反馈影响。我们的工作可能有助于更好地了解成熟脂肪细胞的生物学特性，并可能通过调节胰岛素和胰岛素信号水平来帮助制定抗肥胖策略。