Objective

In a porcine model we demonstrated that high fat fed pigs developed obesity and were protected against post cardiac surgery acute kidney injury compared to lean controls. This is in agreement with recent studies have reported a paradoxical benefit for increased BMI in cardiac surgery. We suspect that better survival rates result in different gene expression pattern in obese pigs.

Methods

Female pigs were fed high fat (n=6) and ctrl (n=6) diets for 12 weeks. Three animals in each group were subjected to either CPB or sham operation, as published in Sleeman et al., 2013. mRNA was isolated from pig hearts, reverse transcribed, labelled and hybridised to Agilent 4x44K chip. Scanned signal was normalised filtered using Agi4x44Preprocess. Improved chip annotation was done with BLAST and differential expression with Limma. Data was analysed with GSEA and Ingenuity Pathway Analysis.

Results

Clustering revealed that diet has the strongest effect on gene expression: 2086 genes were affected when comparing high fat and ctrl animals and expr. of 1170 (ctrl gr.) and 1889 (high fat gr.) was affected when comparing CPB and Sham operation groups. Functional analysis revealed positive association of high fat diet with mitochondrial energy production, hedgehog signaling and tissue remodelling pathways. Negative association was noted for oxidative phosphorylation and muscle contraction genes.

Conclusion

Our analysis identified potential gene sets that are important for tissue preconditioning in obese animals, that include genes regulating mitochondrial function and oxidative stress processes.