Influence of carnitine on the miRNA expression profile in liver and skeletal muscle of growing pigs and its regulatory effects on different target transcripts.

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Recent studies have shown that supplementation of carnitine, the cofactor of the carnitine shuttle system involved in fatty acid metabolism, alters the gene expression profile in liver and skeletal muscle of pigs. Furthermore, our observations demonstrate that carnitine exerts multiple effects on the expression of genes involved in lipid metabolism, glucose uptake and glucose oxidation, the IGF-1/PI3K/Akt-signalling pathway, the protein turnover and apoptosis. Further research will uncover additional mechanisms of carnitine-mediated gene and protein regulation. Presently there are studies using different model organisms modified in their microRNA (miRNA) expression profiles, showing an altered translation of target-transcripts, leading to a repression of protein synthesis which results in variable phenotypic modifications. These changes depend on the species, the breed, the tissue and the corresponding developmental stage of the organism. Recent studies show that nutritional ingredients and / or additives, such as conjugated linoleic acids can affect the miRNA transcriptome. The results of these studies indicate that the investigated feed additives directly alter the expression of specific miRNAs, thereby influencing the post-transcriptional gene regulation resulting in profound changes in metabolism. Consequently, we hypothesize that carnitine affects the miRNA expression profile leading to multiple metabolic changes, as well. This could represent a new molecular mechanism by which carnitine exerts its many effects in the body. To investigate these predicted effects of carnitine, we have to elucidate the following aspects: To what extent does carnitine supplementation or secondary carnitine deficiency modifies the miRNA expression profile in different tissues (liver, skeletal muscle) of pigs (question 1). Secondly, based on the identification of differentially regulated miRNAs from the first experiment, downstream targets which are influenced in their translation by miRNAs and the effects mediated in this way on individual pathways have to be investigated (question 2). Consequently, the planned project contributes to the elucidation of possible, unknown molecular mechanisms of action of carnitine in farm animals, like pigs.