Objective

Cardiac surgery results in an inflammatory response, including activation of vascular endothelium, tissue hypoxia and organ injury. High BMI is a risk factor for cardiovascular death; however recent studies have reported a paradoxical benefit for increased BMI in cardiac surgery. In a model high fat fed pigs were protected against post cardiac surgery acute kidney injury compared to lean controls. This could be due to expression of certain gene sets that precondition against cardiac surgery.

Methods

WT and ApoE-/- mice were fed high fat or control diets for 21 weeks. Animals were sacrificed and organs harvested. Heart ventricles were lysed and proteins analysed by mass spectrometry. Chromatin was isolated from the remaining heart samples and immunoprecipitated with acetylated histone 3 antibodies. qRT-PCR was done with primers for promoter regions of HSPA8, PCCB, TRAP and NFE2L2.

Results

Mice fed high fat diet were heavier (WT: 48.72g±1.52 vs 31.57g±0.46, ApoE-/-: 30.65 g±3.05 vs 29.75 g±0.15); their hearts expressed 19 (WT) and 79 (ApoE-/-) specific proteins and significantly upregulated 40 and 24 proteins, respectively. Analysis indicated that energy production, metabolic and cell adhesion pathways were affected. Analysis of promoters of selected genes revealed chromatin condensation differences between obese and ctrl animals, which corresponded with the expression levels.

Conclusion

Three types of processes are significantly affected by high fat diet that includes mitochondrial gens, fatty acid and amino acid metabolism; and genes encoding proteins responsible for cell-cell adhesion. Computational and lab analysis suggested that epigenetic regulation plays a role in expression changes observed in obese animals.