美国哈佛大学Gkhan S. Hotamisligil、Amir Tirosh等研究人员合作发现，肥胖中肝脏内质网应激的细胞间传递可破坏系统性代谢。该研究于2020年12月18日在线发表于国际一流学术期刊《细胞—代谢》。
研究人员证明，在肝细胞中，内质网应激（ERS）导致连接蛋白43（Cx43）表达增加和细胞间偶联。内质网应激“供体”细胞的共培养导致ERS的细胞间传播以及对ERS-naive“受体”细胞的功能障碍（“旁观者反应”），这可以通过Cx43的遗传或药理抑制来预防。肥胖小鼠的肝细胞能够将ERS传递给瘦小鼠的肝细胞，缺乏肝脏Cx43的小鼠受到饮食诱导的ERS、胰岛素抵抗和肝脂肪变性的保护。
总之，这些结果表明，在肥胖症中，Cx43增加介导的细胞间偶联促使ERS的细胞间传播。这种对营养过剩的新型适应不良反应加剧了组织的ERS负担，促进了肝脂肪变性并损害了全身性葡萄糖代谢。
据介绍，ERS在肥胖相关的胰岛素抵抗中具有病理生理作用。然而，对ERS的组织协调反应仍不清楚。Cx43介导的细胞间交流增加与组织对各种慢性应激的适应性反应有关。
附：英文原文
Title: Intercellular Transmission of Hepatic ER Stress in Obesity Disrupts Systemic Metabolism
Author: Amir Tirosh, Gurol Tuncman, Ediz S. Calay, Moran Rathaus, Idit Ron, Amit Tirosh, Abdullah Yalcin, Yankun G. Lee, Rinat Livne, Sophie Ron, Neri Minsky, Ana Paula Arruda, Gkhan S. Hotamisligil
Issue&Volume: 2020-12-18
Abstract: Endoplasmic reticulum stress (ERS) has a pathophysiological role in obesity-associatedinsulin resistance. Yet, the coordinated tissue response to ERS remains unclear. Increasedconnexin 43 (Cx43)-mediated intercellular communication has been implicated in tissue-adaptiveand -maladaptive response to various chronic stresses. Here, we demonstrate that inhepatocytes, ERS results in increased Cx43 expression and cell-cell coupling. Co-cultureof ER-stressed “donor” cells resulted in intercellular transmission of ERS and dysfunctionto ERS-naive “recipient” cells (“bystander response”), which could be prevented bygenetic or pharmacologic suppression of Cx43. Hepatocytes from obese mice were ableto transmit ERS to hepatocytes from lean mice, and mice lacking liver Cx43 were protectedfrom diet-induced ERS, insulin resistance, and hepatosteatosis. Taken together, ourresults indicate that in obesity, the increased Cx43-mediated cell-cell coupling allowsintercellular propagation of ERS. This novel maladaptive response to over-nutritionexacerbates the tissue ERS burden, promoting hepatosteatosis and impairing whole-bodyglucose metabolism.
DOI: 10.1016/j.cmet.2020.11.009
Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30604-5
Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
官方网址：https://www.cell.com/cell-metabolism/home
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本期文章：《细胞—代谢》：Online/在线发表
