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DOI: 10.1055/s-0035-1547608
Identification of high fat diet induced inflammatory gene networks associated with suppression of anti-inflammatory phospholipids in human adipose tissue in the NUGAT (Nutrigenomics Analysis in Twins) study
[08:10 – 08:20]
Aim: Lipid metabolism and signaling might be either controlled genetically or by environmental factors. The aim of the study was to correlate lipidomic and genomic data of human subjects to identify specific gene-modules responsible for the regulation or connected with the function of specific lipid metabolites.
Methods: In the NUGAT-Study 46 healthy mono- and dizygotic twin-pairs first were standardized for their nutritional behavior by a carbohydrate-rich low-fat diet for 6 weeks (LF), immediately followed by a high-fat diet for 1 week (HF1) and additional 5 weeks (HF6). At each CID periumbilical fat biopsies were taken for determination of gene expression on Agilent 8 × 40K gene micro Arrays. Plasma was measured for lipid metabolites and cytokines (ELISA). Weighted gene Co-Expression Network Analysis (WGCNA) and regularized Canonical Covariance Analysis (rCCA) were used for identification of co-expressed gene-networks and their correlation with lipidome data.
Results: By analysis of the 5000 strongest regulated genes a gene-module was identified to be highly correlated (p < 0.00001 to 0.0006) with CRP (r2= 0.31), VEGF (r2= 0.39), IL1ra (r2= 0.35) and PP (r2= 0.3) and highly associated (r2=-0.32, p < 0.0004) with an anti-inflammatory/anti-bacterial lysophosphatidylethanolamine specimen (LPE). In almost all volunteers LPE decreased during the high-fat diet (-0.50 ± 0.70 mmol/L), as well as IL1ra, while CRP and VEGF increased. Application of rCCA showed an increasing association of a set of genes involved in lysophosphatidic acid (LPA) receptor signaling with the decreasing concentrations of LPE specimen.
Conclusion: Our data show for the first time in humans that high-fat diet induces inflammation by remodeling lipid biosynthetic pathways reducing anti-inflammatory and increasing inflammatory signaling. Specifically we identify downregulation of the anti-inflammatory phospholipid LPE and increasing synchronization of LPE concentration with gene expression patterns as a mediator of inflammatory processes in the adipose tissue.