Visceral Fat Accumulation Induced by a High‐fat Diet Causes the Atrophy of Mesenteric Lymph Nodes in Obese Mice

Abstract

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.

Effects of feeding fish oil on mesenteric lymph node cytokine responses in obese leptin receptor-deficient JCR:LA-cp rats

“…The authors suggested that factors emanating from the mesenteric fat, such as free fatty acids, induced apoptosis of lymphocytes residing in MLN. 11 In this study, we also show that immunity in gut-associated lymph tissue is altered. More specifically, MLN immune cells of obese JCR:LA-cp rats produced higher amounts of IL-1b, suggesting a heightened inflammatory response as compared with peripheral immune cells and are most likely influenced by the inflammatory environment of the mesenteric adipose tissue.…”

“…1 To date, only one study has investigated the impact of obesity on MLN immune cell function. Kim et al 11 reported that high fat-fed mice had smaller MLN and subsequently fewer immune cells. The authors suggested that factors emanating from the mesenteric fat, such as free fatty acids, induced apoptosis of lymphocytes residing in MLN.…”

“…Only one study has investigated mesenteric lymph node (MLN) immune cell function in an obese rodent. Kim et al 11 reported atrophy of MLN, and a fewer total number of lymphocytes were present in MLN in high fat-fed mice. Collectively, research suggests an effect of obesity/visceral fat on immune cells located in MLN and vice versa; however, the ability of these immune cells to respond to stimulation has not been assessed.…”

Metabolic and immunomodulatory effects of n-3 fatty acids are different in mesenteric and epididymal adipose tissue of diet-induced obese mice

“…Therefore, the observed high levels for OPN in MAT and EAT from HF/n-3 mice could be derived from T cells and/or adipocytes. It is important to note that MAT includes MLN, which are involved in immune response, whereas EAT does not contain lymph nodes (32,52). MLN can enlarge due to the expansion of MLN immune cells upon immune responses of the body.…”

Serum lipid profile and hepatic evaluation in mice fed diet containing pequi nut or pulp (Caryocar brasiliense Camb.)

“…Therefore, the highest energetic intake resulted in the greater rate of weight gain observed in animals fed a diet containing pequi (CHARRONDIERE et al, 2004;LIMA et al, 2007;STRIJBOSCH et al, 2008). Moreover, the intake of a high-fat diet has been associated with overweight in mice, thus the higher weight gain in the animals in the experimental groups can be the result of high lipid content of pequi added to diet (KIM et al, 2008;HONG et al, 2009). …”