Full Transcriptome Analysis of the Liver of Rats Receiving the Complex of L-Carnitine and Resveratrol in the Composition of a Standard or Hypercaloric Diet

Abstract

The use of resveratrol and L-carnitine (RC) in the complex as components of dietary products and food supplements is considered a potential approach to the dietary therapy of obesity and associated pathologies. However, the interactions between these bioactive substances upon ingestion, particularly their combined effects on global gene expression patterns, remain poorly understood. We investigated the hepatic transcriptome in male Wistar rats fed a control diet (CD) or a high-fat/high-carbohydrate diet (HFCD), supplemented with low (RCl) or high (RCh) dose RC for 64 days. HFCD altered the expression of 757 genes, while HFCD with RC induced more modest changes (179–243 genes). A key finding was a significant negative correlation between gene expression changes induced by HFCD and RC within the HFCD, indicating a compensatory effect of the supplement. Only two genes, Asns and RT1-CE10, responded to both RC doses in both diets. Bioinformatics analysis revealed that RC targeted four metabolic pathways (KEGGs) also disrupted by HFCD: drug and xenobiotic metabolism by cytochrome P450, retinol metabolism, and steroid hormone biosynthesis. The PPAR signaling pathway was altered by both RC doses in CD-fed rats and by RCh in HFCD-fed rats. These findings identify xenobiotic detoxification, retinoid/steroid metabolism, and fatty acid oxidation as key transcriptomic targets through which the RC supplement may counteract diet-induced obesity. The interaction between resveratrol and L-carnitine at the gene expression level should be considered when developing combined dietary supplements.