P515The effects of short time high fat diet & gender on heart metabolism: A 1H NMR metabolomic study

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Abstract

Dislipemia is a risk factor for cardiovascular diseases through the accumulation of cholesterol esters in coronary atherosclerotic plaques and indirectly because it can induce type-2 diabetes that it is, in turn, another cardiovascular risk factor. The formation of atherosclerotic plaques is a complex and much studied process that usually takes years until symptoms like angina or an acute coronary syndrome appear.

However, little is known about possible short term effects of a high fat diet (HFD). The objective of our work was to investigate if HFD induced changes in heart metabolism after just two weeks and the interaction with gender in a mice model.

Mice were fed a HFD (n=12) or control chow diet (n=12) for two weeks, each group consisted in 7 males and 5 females. After two weeks animals were euthanised and tissues (heart, liver, brain) extracted using methanol:chloroform; blood was collected from the heart left ventricle, left to coagulate and serum separated by centrifugation.

1H NMR spectra were acquired on a Bruker Avance 400 spectrometer using a fully relaxed pulse-and-acquire sequence for tissues or CPMG with an effective T2 delay of 32 ms in the case of serum. Spectra were analyzed using pattern recognition with SIMCA-P software.

In the case of heart, it was possible to obtain discriminant models able to differentiate between HFD and control animals (Q2=0,383); gender also had a clear effect on heart metabolism as it was possible to differentiate between male and female animals with better predictive capacity than HFD (Q2=0,470). A 4 group model differentiating gender and diet was also statistical significant (Q2=0,149). HFD had clear effects on liver and serum metabolism but not on the brain while gender affected brain and serum metabolic profiles.

HFD hearts contained more alanine and less glutamate and phosphocreatine than mice fed with control diet. High levels of alanine could be indicative of faster anaerobic glycolisis turnover. Also, control animals have relatively elevated creatine and glutamate suggestive of a better energy state.

Females had higher levels of acetate, that bound to coenzime A, is central to carbohydrate and lipid metabolism; thus higher levels of acetate could be indicative of differential use of substrates as energy sources between male and female animals.

In conclusion, short term HFD treatment affects heart metabolism; this may have implications in diseases like heart failure and also affect the response to ischemia-reperfusion injury.

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