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

Sara L Svahn,Eduard Peris,Maria E Johansson,Intawat Nookaew,Britt G Gabrielsson,Ann-Sofie Sandberg,Louise Grahnemo,John-Olov Jansson,Ingrid Wernstedt Asterholm,Jens Nielsen,Leif Väremo

doi:10.1371/journal.pone.0155099

Sara L Svahn, Eduard Peris + Show 9 more

Open Access

https://doi.org/10.1371/journal.pone.0155099

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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.

Highlights

Fatty acids are a heterogeneous group of macronutrients that can be divided into saturated fatty acids (SFA), monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA)
To get an overall assessment of the effects of the diets on the different tissues, we investigated differentially expressed genes in three comparisons: mice fed high fat diet (HFD)-S vs. low fat diet (LFD), HFD rich in PUFA (HFD-P) vs. LFD and HFD-P vs. HFD-S
skeletal muscle (SKM) and bone marrow cells (BMC) were relatively inert to the diets, whereas the two adipose tissues (WAT and brown adipose tissue (BAT)) were mainly affected by HFDs per se

Summary

Introduction

Fatty acids are a heterogeneous group of macronutrients that can be divided into saturated fatty acids (SFA), monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA). It has been shown that these three types of fat affect the body and the immune system differently, especially in the pathological inflammatory responses associated with metabolic disease [1,2,3]. Low fat diets (LFDs) were widely recommended to maintain a healthy body weight. Current dietary recommendations are less focused on the amount of fat and more on the fatty acid composition [4,5]. In several observational studies, the amount of dietary fat has only been associated with minor or negligible effects on cardiometabolic diseases, such as cardiovascular diseases and type-2 diabetes mellitus, while the dietary fatty acid composition appears to be more important [5,6]. It has been shown that replacing the energy from SFA with the equivalent energy from unsaturated fatty acids reduces the risk of developing coronary heart disease [5,6]

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