Characterization of dietary protein-dependent amino acid metabolism by linking free amino acids with transcriptional profiles through analysis of correlation

Abstract

This study aims to characterize diet-dependent amino acid metabolism by linking profiles of amino acids concentrations (“aminograms”) with transcript datasets through the analysis of correlation. We used a dietary model of protein restriction-to-excess, where rats were fed diets with different levels of casein (5, 10, 15, 20, 30, 50, and 70%) for 2 wk. Twenty-five different amino acids in the plasma, liver, kidney, small intestine, and muscle and 71 gene transcripts in these compartments were measured together with general physiological variables. Under low-protein diet (LPD) conditions, the plasma aminogram for EAA was similar to that of the liver and the small intestine, respectively. Under the high-protein diet (HPD), however, the plasma aminogram for EAA became like that of muscle, while that of NEAA was similar with that of both liver and muscle. To assess the impact of gene expressions in each tissue on the plasma aminograms, correlations were obtained between aminograms and transcripts in each tissue under a diet with different protein levels. Based on the correlations obtained, amino acids and transcripts were systematically connected and then a metabolite-to-gene network was constructed for either LPD or HPD condition. The networks obtained and some other metabolically meaningful relationships such as ureagenesis and serine metabolism clearly illustrated activation of either body protein breakdown with LPD or amino acid catabolism with HPD.