中文摘要：
血脂异常是心血管疾病的主要驱动因素。巨噬细胞清除过量脂质的能力使其在这一过程中的作用愈加重要，理解巨噬细胞脂质代谢的机制是开发新治疗方法的关键。在这项研究中，我们探讨了脂肪组织巨噬细胞如何调节餐后胆固醇运输。单细胞RNA测序和保护性骨髓嵌合体展示了脂质摄入导致一群表达Lyve1、Tim4和ABCA1的驻留巨噬细胞特异性转录激活。阻断磷脂酰丝氨酸受体Tim4抑制了溶酶体激活以及高脂餐后高密度脂蛋白胆固醇的释放。这两种效应均可通过氯喹重现，这是一种溶酶体功能抑制剂。此外，荷兰氯膦酸盐脂质体介导的巨噬细胞耗竭提示Tim4驻留脂肪组织巨噬细胞在此过程中的作用。因此，这些数据显示Tim4是餐后胆固醇运输和脂肪组织巨噬细胞功能的关键调节因子，并可能代表治疗血脂异常的新途径。
英文摘要：
Dyslipidemia is a main driver of cardiovascular diseases. The ability of macrophages to scavenge excess lipids implicate them as mediators in this process and understanding the mechanisms underlying macrophage lipid metabolism is key to the development of new treatments. Here, we investigated how adipose tissue macrophages regulate post-prandial cholesterol transport. Single-cell RNA sequencing and protected bone marrow chimeras demonstrated that ingestion of lipids led to specific transcriptional activation of a population of resident macrophages expressing Lyve1, Tim4, and ABCA1. Blocking the phosphatidylserine receptor Tim4 inhibited lysosomal activation and the release of post-prandial high density lipoprotein cholesterol following a high fat meal. Both effects were recapitulated by chloroquine, an inhibitor of lysosomal function. Moreover, clodronate-mediated cell-depletion implicated Tim4+ resident adipose tissue macrophages in this process. Thus, these data indicate that Tim4 is a key regulator of post-prandial cholesterol transport and adipose tissue macrophage function and may represent a novel pathway to treat dyslipidemia.
论文信息：
论文题目：Role of Tim4 in the regulation of ABCA1+ adipose tissue macrophages and post-prandial cholesterol levels
期刊名称：Nature Communications
时间期卷：12, Article number: 4434 (2021)
在线时间：2021年7月21日
DOI：doi.org/10.1038/s41467-021-24684-7
产品信息：
货号：C-010
规格：10ml
品牌：Liposoma
产地：荷兰
名称：Clodronate Liposomes
办事处：Target Technology(靶点科技)
Clodronate Liposomes氯膦酸盐脂质体清除肝脏和腹腔巨噬细胞，疾病模型为：高脂肪诱导的肥胖模型。脂肪组织（AT）的主要功能是储存脂质以建立能量储备；脂肪细胞专业化于摄取膳食脂质并将其储存为甘油三酯（TGs）。在以低热量食物为主的饮食背景下，一顿特别丰富的脂质，因此成为脂肪细胞增加其TG储存的生理机会。尽管对脂肪组织巨噬细胞（ATMs）在肥胖代谢适应中的作用的理解日益加深，关于ATMs在脂质富含的餐后脂质代谢和脂肪储存调节中的作用却知之甚少。荷兰Liposoma巨噬细胞清除剂Clodronate Liposomes见刊于Nature Communications：Tim4在调节ABCA1+脂肪组织巨噬细胞和餐后胆固醇水平中的作用。
Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体的材料和方法：
Mice were kept on control diet (11 kcal%Fat and corn starch, Research diet, D12328i). For overnight high fat feeding, mice were given HFD (58Kcal%Fat and sucrose, Research diet, D12331i) at 4 p.m. and were culled the next morning at 9 a.m. For Tim4 blocking, mice were i.p. injected, 72 h and on the day prior to the overnight HFD, with 100 μl of phosphate-buffered saline (PBS) containing either 200 μg of anti-Tim4 IgG2a (clone RMT4-53, Rat IgG2a, BE0171, BioXCell) or 200 μg of rat IgG2a control (BE0089, BioXCell). Mice were injected i.p. with 1 mg of chloroquine (Sigma) in 200 μl of PBS 72 h and on the day prior to the overnight HFD. Mice were injected with 200 μg clodronate liposomes (Liposoma, the Netherlands) in 200 μl PBS 48 h prior to overnight HFD.
材料和方法文献截图：
