Abstract
IntroductionObesity 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.MethodsAdult 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.ResultsHigh 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.ConclusionsObesity 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.
Highlights
Obesity is a major cause of morbidity and mortality resulting in pathologic changes in virtually every organ system
We show that C57B6-6J mice fed a high fat diet become obese over a relatively short period of time, but that these mice have markedly decreased lymphatic fluid flow and impaired migration of dendritic cells (DCs) to draining lymph nodes
Our findings strongly suggest that diet induced obesity (DIO) results in significant pathologic changes in the lymphatic collecting system and lymph nodes, and that at least some of these changes are dependent on T or B cell inflammatory reactions
Summary
Obesity is a major cause of morbidity and mortality resulting in pathologic changes in virtually every organ system. The cardiovascular system has been a focus of intense study, the effects of obesity on the lymphatic system remain essentially unknown. Obesity results in pathologic changes in virtually every organ system and is a leading cause of morbidity and mortality. The effects of obesity on the cardiovascular system have been intensely studied, there is comparably little known about how dietary changes or adipose accumulation impact the lymphatic system. This is important since the lymphatic system plays a critical role in returning interstitial fluid and lipids to the cardiovascular system. Understanding how obesity and dietary changes regulate lymphatic function and immune responses is important and may provide important insights into the pathology of obesity
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