Six Tissue Transcriptomics Reveals Specific Immune Suppression in Spleen by Dietary Polyunsaturated Fatty Acids

Abstract

Dietary polyunsaturated fatty acids (PUFA) are suggested to modulate immune function, but the effects of dietary fatty acids composition on gene expression patterns in immune organs have not been fully characterized. In the current study we investigated how dietary fatty acids composition affects the total transcriptome profile, and especially, immune related genes in two immune organs, spleen (SPL) and bone marrow cells (BMC). Four tissues with metabolic function, skeletal muscle (SKM), white adipose tissue (WAT), brown adipose tissue (BAT), and liver (LIV), were investigated as a comparison. Following 8 weeks on low fat diet (LFD), high fat diet (HFD) rich in saturated fatty acids (HFD-S), or HFD rich in PUFA (HFD-P), tissue transcriptomics were analyzed by microarray and metabolic health assessed by fasting blood glucose level, HOMA-IR index, oral glucose tolerance test as well as quantification of crown-like structures in WAT. HFD-P corrected the metabolic phenotype induced by HFD-S. Interestingly, SKM and BMC were relatively inert to the diets, whereas the two adipose tissues (WAT and BAT) were mainly affected by HFD per se (both HFD-S and HFD-P). In particular, WAT gene expression was driven closer to that of the immune organs SPL and BMC by HFDs. The LIV exhibited different responses to both of the HFDs. Surprisingly, the spleen showed a major response to HFD-P (82 genes differed from LFD, mostly immune genes), while it was not affected at all by HFD-S (0 genes differed from LFD). In conclusion, the quantity and composition of dietary fatty acids affected the transcriptome in distinct manners in different organs. Remarkably, dietary PUFA, but not saturated fat, prompted a specific regulation of immune related genes in the spleen, opening the possibility that PUFA can regulate immune function by influencing gene expression in this organ.

Dietary Polyunsaturated Fatty Acids Promote Neutrophil Accumulation in the Spleen by Altering Chemotaxis and Delaying Cell Death

“…This pattern is in accordance with the findings of our previous microarray analysis performed in the spleen, bone marrow, skeletal muscle, white adipose tissue, and brown adipose tissue from mice fed LFD, HFD-S, or HFD-P (20). In such an analysis, bone marrow and skeletal muscle were relatively unchanged by the diets, whereas both white and brown adipose tissues were similarly affected by HFD-S and HFD-P.…”

“…We have previously reported that mice fed HFD-S have an increased liver size compared with mice fed LFD and HFD-P after 8 weeks of diet (20). However, after 4 weeks of diet, the size of the liver was not altered by either HFD-S or HFD-P ( Fig.…”

“…We have previously reported the results of a complete microarray analysis of several tissues, including the spleen, from mice fed LFD, HFD-S, and HFD-P (20). When extracting gene expression data corresponding to chemokines or chemokine receptors from that analysis (20), we found no differences in the expression levels of CXCR2 in the spleens from mice fed LFD, HFD-S, and HFD-P ( Fig. S3A).…”

“…HFD-P (catalog number D09020505; Research Diets, USA) has the same caloric content and the same proportion of nutrients as HFD-S, but 69% of the lard (a saturated fat) was exchanged for menhaden oil (a polyunsaturated fat). A more detailed list of the composition of the diets can be found in our previous publications (20). Food was exchanged three times per week for a total duration of 4 or 8 weeks.…”

Partitioning of Rumen‐Protected n‐3 and n‐6 Fatty Acids is Organ‐Specific in Growing Angus Heifers

“…Nevertheless, feeding a diet rich in n-3 FA to fattening pigs led to a suppression of pro-inflammatory markers and an increased gene expression of detoxifying enzymes in the spleen (Taranu et al, 2014). Studies in mice confirmed that the spleen is one of the target organs for the anti-inflammatory effects of n-3 FA (Soni et al, 2017;Svahn et al, 2016). In the lung, feeding a diet rich in n-3 FA to pigs attenuated the response to endotoxin injection compared to groups fed diets rich in n-6 FA (Murray et al, 1993).…”