Endoplasmic reticulum stress in adipose tissue augments lipolysis.
Endoplasmic reticulum stress in adipose tissue augments lipolysis.
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DOI：
10.1111/jcmm.12384
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发表时间：
2015-01
影响因子：
5.3
通讯作者：
Jeschke MG
中科院分区：
文献类型：
--
作者：
Bogdanovic E;Kraus N;Patsouris D;Diao L;Wang V;Abdullahi A;Jeschke MG
内质网 (ER) 是一种对蛋白质合成和折叠、脂质合成和 Ca2+ 稳态非常重要的细胞器。因此，内质网应激或功能障碍影响许多细胞过程，并被认为是多种病理生理状况的促成因素。 Tunicamycin 在体外和体内诱导各种细胞类型的 ER 应激。在小鼠中，给予衣霉素的一个标志是在 24-48 小时内形成脂肪肝，并伴有肝脏 ER 应激。我们假设衣霉素会诱导脂肪组织内质网应激，导致脂肪分解增加，随后导致肝脏脂肪浸润和肝肿大。我们的结果表明，腹膜内施用衣霉素迅速诱导脂肪组织中的内质网应激反应，该反应与循环游离脂肪酸（FFA）和甘油的增加以及脂肪组织质量和脂滴大小的减少相关。此外，我们发现除了肝脏的脂肪浸润和肝肿大外，心脏、骨骼肌和肾脏也存在脂质堆积。为了在临床环境中证实我们的发现，我们检查了烧伤患者的脂肪组织，其中脂肪分解的增加和脂肪肝的发展已得到充分记录。我们发现烧伤患者在脂肪组织内表现出显着的内质网应激，并且内质网应激会增强培养的人类脂肪细胞中的脂肪分解。我们的结果表明，内质网应激诱导的脂肪组织脂解作用可能是导致循环 FFA 增加和脂肪浸润到其他器官的潜在机制。
The endoplasmic reticulum (ER) is an organelle important for protein synthesis and folding, lipid synthesis and Ca2+ homoeostasis. Consequently, ER stress or dysfunction affects numerous cellular processes and has been implicated as a contributing factor in several pathophysiological conditions. Tunicamycin induces ER stress in various cell types in vitro as well as in vivo. In mice, a hallmark of tunicamycin administration is the development of fatty livers within 24–48 hrs accompanied by hepatic ER stress. We hypothesized that tunicamycin would induce ER stress in adipose tissue that would lead to increased lipolysis and subsequently to fatty infiltration of the liver and hepatomegaly. Our results show that intraperitoneal administration of tunicamycin rapidly induced an ER stress response in adipose tissue that correlated with increased circulating free fatty acids (FFAs) and glycerol along with decreased adipose tissue mass and lipid droplet size. Furthermore, we found that in addition to fatty infiltration of the liver as well as hepatomegaly, lipid accumulation was also present in the heart, skeletal muscle and kidney. To corroborate our findings to a clinical setting, we examined adipose tissue from burned patients where increases in lipolysis and the development of fatty livers have been well documented. We found that burned patients displayed significant ER stress within adipose tissue and that ER stress augments lipolysis in cultured human adipocytes. Our results indicate a possible role for ER stress induced lipolysis in adipose tissue as an underlying mechanism contributing to increases in circulating FFAs and fatty infiltration into other organs.
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影响因子：
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作者：
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发表时间：
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影响因子：
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作者：
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影响因子：
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作者：
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