Objective: A high intake of fat in the diet plays a crucial role in promoting obesity and obesity-related pathologies, and especially visceral obesity is closely associated with obesity-related complications. Because adipose tissue is anatomically associated with lymph nodes, the secondary lymphoid organ, we hypothesized that fat tissue-derived factors may influence the cellularity of lymphoid tissue embedded in fat.
Methods and procedures: Mesenteric and inguinal lymph nodes were isolated from obese mice fed a high-fat diet and control mice fed a regular diet. T-cell population, activation state, and the extent of apoptosis were determined by flow cytometric analysis or terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) assay.
Results: The weight of mesenteric lymph nodes and the total number of lymphoid cells in the obese mice significantly decreased compared with those in the control mice; however, no change was observed in the weight of inguinal lymph nodes. The numbers of CD4(+) and CD8(+) T cells in the mesenteric lymph nodes of obese mice significantly decreased compared with those of the control. Enhanced T-cell activation and apoptosis were observed in the mesenteric lymph node cells of the obese mice. The treatment of lymph node cells with free fatty acids, oxidative stress, and chylomicrons, which are obesity-related factors, resulted in lymph node T-cell activation and apoptosis.
Discussion: These results suggest that visceral fat accumulation with a high-fat diet can cause the atrophy of mesenteric lymph nodes by enhancing activation-induced lymphoid cell apoptosis. Dietary fat-induced visceral obesity may be crucial for obesity-related immune dysfunction.