Adipocyte Death Preferentially Induces Liver Injury and Inflammation Through the Activation of Chemokine (C-C Motif) Receptor 2-Positive Macrophages and Lipolysis.
脂肪细胞死亡通过趋化因子 (C-C 基序) 受体 2 阳性巨噬细胞和脂肪分解的激活,优先诱导肝损伤和炎症。

摘要

Adipocyte death occurs under various physiopathological conditions, including obesity and alcohol drinking, and can trigger organ damage particularly in the liver, but the underlying mechanisms remain obscure. To explore these mechanisms, we developed a mouse model of inducible adipocyte death by overexpressing the human CD59 (hCD59) on adipocytes (adipocyte-specific hCD59 transgenic mice). Injection of these mice with intermedilysin (ILY), which rapidly lyses hCD59 expressing cells exclusively by binding to the hCD59 but not mouse CD59, resulted in the acute selective death of adipocytes, adipose macrophage infiltration, and elevation of serum free fatty acid (FFA) levels. ILY injection also resulted in the secondary damage to multiple organs with the strongest injury observed in the liver, with inflammation and hepatic macrophage activation. Mechanistically, acute adipocyte death elevated epinephrine and norepinephrine levels and activated lipolysis pathways in adipose tissue in a chemokine (C-C motif) receptor 2-positive (CCR2+ ) macrophage-dependent manner, which was followed by FFA release and lipotoxicity in the liver. Additionally, acute adipocyte death caused hepatic CCR2+ macrophage activation and infiltration, further exacerbating liver injury. Conclusion: Adipocyte death predominantly induces liver injury and inflammation, which is probably due to the superior sensitivity of hepatocytes to lipotoxicity and the abundance of macrophages in the liver.

译文

脂肪细胞死亡发生在各种病理生理条件下,包括肥胖和饮酒,并可能引发器官损伤,尤其是在肝脏,但潜在的机制仍然不清楚。为了探索这些机制,我们通过在脂肪细胞 (脂肪细胞特异性 hCD59 转基因小鼠) 上过量表达人 CD59 (hCD59),建立了一个诱导脂肪细胞死亡的小鼠模型。将这些小鼠注射中介溶素 (ILY),这种溶素能通过与 hCD59 结合而快速溶解 hCD59 表达细胞,但不能与小鼠 CD59 结合,导致脂肪细胞急性选择性死亡,脂肪巨噬细胞浸润, 和血清游离脂肪酸 (FFA) 水平的升高。ILY 注射还导致了肝脏中损伤最强的多器官的继发性损伤,包括炎症和肝巨噬细胞的激活。从机制上来说,急性脂肪细胞死亡提高了肾上腺素和去甲肾上腺素的水平,并且激活了脂肪组织中趋化因子 (C-C 基序) 受体 2 阳性 (CCR2) 巨噬细胞依赖的脂肪分解途径, 随后是肝脏中 FFA 释放和脂毒性。此外,急性脂肪细胞死亡导致肝 CCR2 巨噬细胞活化和浸润,进一步加剧肝损伤。结论: 脂肪细胞死亡主要诱导肝损伤和炎症反应,这可能是由于肝细胞对脂毒性的高度敏感性和巨噬细胞在肝脏中的丰度。

Adipocyte

内分泌 细胞 临床研究术语
概述  :  

脂肪细胞源自间充质干细胞,它们通过脂肪形成而产生脂肪细胞。在细胞培养中,脂肪细胞还可以形成成骨细胞,心肌细胞和其他细胞类型。脂肪组织有两种类型,白色脂肪组织(WAT)和棕色脂肪组织(BAT),分别也称为白色脂肪和棕色脂肪,并且包含两种类型的脂肪细胞。结构白色脂肪细胞或单泡细胞含有大的脂质滴,被细胞质层包围,所述核变平,并且位于外围。一个典型的脂肪细胞的直径为0.1毫米,其中一些是该大小的两倍,而有些是该大小的一半。储存的脂肪为半液态,主要由甘油三酸酯和胆固醇酯组成。白色脂肪细胞分泌许多可作为

adipocyte   英 /'ædipəu,sait/

释    义   n. [组织] 脂肪细胞

例    句   An adipocyte is an animal tissue cell specialized for the synthesis and storage of fat.脂肪细胞是一种专门合成和储藏脂肪的动物组织细胞。

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