Obesity Impairs Lymphatic Fluid Transport and Dendritic Cell Migration to Lymph Nodes
Obesity Impairs Lymphatic Fluid Transport and Dendritic Cell Migration to Lymph Nodes
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DOI：
10.1371/journal.pone.0070703
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发表时间：
2013-08-12
期刊：
影响因子：
3.7
通讯作者：
Mehrara, Babak J.
中科院分区：
文献类型：
--
作者：
Weitman, Evan S.;Aschen, Seth Z.;Mehrara, Babak J.
简介：肥胖是导致几乎所有器官系统病理改变的发病率和死亡率的主要原因。尽管心血管系统一直是密集研究的焦点，但肥胖对淋巴系统的影响基本上仍然未知。本研究的目的是确定饮食性肥胖（DIO）对淋巴系统的病理后果。方法：以成年雄性野生型小鼠和RAG C57B6-6J小鼠为研究对象，分别饲喂高脂（60%）和正常饲料8-10周，分析其淋巴运输能力。此外，我们还评估了树突状细胞（dc）向局部淋巴结的迁移、淋巴结结构和淋巴结细胞组成。结果：高脂饮食导致野生型和RAG小鼠肥胖，并显著损害淋巴液运输和淋巴结摄取；有趣的是，肥胖野生型而非肥胖RAG小鼠的dc向外周淋巴结的迁移明显受损。肥胖还导致淋巴结的宏观和微观解剖结构发生显著变化，表现为腹股沟淋巴结大小明显减少（3.4倍），淋巴结淋巴管数量减少（1.6倍），B细胞滤泡模式丧失，CCL21表达梯度失调。最后，肥胖导致淋巴结T细胞数量明显减少，B细胞和巨噬细胞数量增加。结论：肥胖对淋巴运输、DC细胞迁移和淋巴结结构有显著的负面影响。T细胞和B细胞炎症反应的丧失不能保护淋巴液运输受损，但保留DC迁移能力。未来的研究需要确定饮食、肥胖和淋巴系统之间的相互作用如何调节肥胖的全身并发症。
Introduction: Obesity is a major cause of morbidity and mortality resulting in pathologic changes in virtually every organ system. Although the cardiovascular system has been a focus of intense study, the effects of obesity on the lymphatic system remain essentially unknown. The purpose of this study was to identify the pathologic consequences of diet induced obesity (DIO) on the lymphatic system.Methods: Adult male wild-type or RAG C57B6-6J mice were fed a high fat (60%) or normal chow diet for 8-10 weeks followed by analysis of lymphatic transport capacity. In addition, we assessed migration of dendritic cells (DCs) to local lymph nodes, lymph node architecture, and lymph node cellular make up.Results: High fat diet resulted in obesity in both wild-type and RAG mice and significantly impaired lymphatic fluid transport and lymph node uptake; interestingly, obese wild-type but not obese RAG mice had significantly impaired migration of DCs to the peripheral lymph nodes. Obesity also resulted in significant changes in the macro and microscopic anatomy of lymph nodes as reflected by a marked decrease in size of inguinal lymph nodes (3.4-fold), decreased number of lymph node lymphatics (1.6-fold), loss of follicular pattern of B cells, and dysregulation of CCL21 expression gradients. Finally, obesity resulted in a significant decrease in the number of lymph node T cells and increased number of B cells and macrophages.Conclusions: Obesity has significant negative effects on lymphatic transport, DC cell migration, and lymph node architecture. Loss of T and B cell inflammatory reactions does not protect from impaired lymphatic fluid transport but preserves DC migration capacity. Future studies are needed to determine how the interplay between diet, obesity, and the lymphatic system modulate systemic complications of obesity.