Autophagy regulates inflammation in adipocytes.
Autophagy regulates inflammation in adipocytes.
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DOI：
10.1016/j.bbrc.2011.11.114
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发表时间：
2012-01
影响因子：
3.1
通讯作者：
Takeshi Yoshizaki;Chisato Kusunoki;Motoyuki Kondo;M. Yasuda;S. Kume;K. Morino;Osamu Sekine;S. Ugi;T. Uzu;Y. Nishio;A. Kashiwagi;H. Maegawa
中科院分区：
文献类型：
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作者：
Takeshi Yoshizaki;Chisato Kusunoki;Motoyuki Kondo;M. Yasuda;S. Kume;K. Morino;Osamu Sekine;S. Ugi;T. Uzu;Y. Nishio;A. Kashiwagi;H. Maegawa
自噬是细胞维持和存活的重要过程，稳态低水平的自噬对细胞内细胞器和蛋白质至关重要。在胰岛素抵抗性脂肪细胞中，各种功能障碍/受损的分子、细胞器、蛋白质和终产物积累。然而，自噬的作用（特别是自噬是否被激活）知之甚少。在本研究中，我们发现在胰岛素抵抗小鼠的脂肪组织和肥大的3 T3-L1脂肪细胞中，自噬被抑制。同样在肥大脂肪细胞中，自噬相关基因表达，如LAMP 1，LAMP 2和Atg 5减少，而炎症相关基因的基因表达，如MCP-1，IL-6和IL-1β增加。为了确定自噬抑制是否与炎症有关，我们使用自噬抑制剂3-甲基腺嘌呤来抑制自噬。我们的研究结果表明，这种抑制导致炎症基因表达的增加，并导致内质网（ER）应激（这可以通过ER应激抑制剂，牛磺熊去氧胆酸治疗减弱）。相反，炎症基因表达水平降低自噬的激活或抑制ER应激。结果表明，自噬的抑制通过ER应激增加炎症反应，并且还定义了自噬作为全身性胰岛素抵抗中脂肪细胞炎症的重要调节剂的新作用。
Autophagy is an essential process for both the maintenance and the survival of cells, with homeostatic low levels of autophagy being critical for intracellular organelles and proteins. In insulin resistant adipocytes, various dysfunctional/damaged molecules, organelles, proteins, and end-products accumulate. However, the role of autophagy (in particular, whether autophagy is activated or not) is poorly understood. In this study we found that in adipose tissue of insulin resistant mice and hypertrophic 3T3-L1 adipocytes autophagy was suppressed. Also in hypertrophic adipocytes, autophagy-related gene expression, such as LAMP1, LAMP2, and Atg5 was reduced, whereas gene expression in the inflammatory-related genes, such as MCP-1, IL-6, and IL-1β was increased. To find out whether suppressed autophagy was linked to inflammation we used the autophagy inhibitor, 3-methyladenine, to inhibit autophagy. Our results suggest that such inhibition leads to an increase in inflammatory gene expression and causes endoplasmic reticulum (ER) stress (which can be attenuated by treatment with the ER stress inhibitor, Tauroursodeoxycholic Acid). Conversely, the levels of inflammatory gene expression were reduced by the activation of autophagy or by the inhibition of ER stress. The results indicate that the suppression of autophagy increases inflammatory responses via ER stress, and also defines a novel role of autophagy as an important regulator of adipocyte inflammation in systemic insulin resistance.