Co-Administration of Trans-Resveratrol and L-Carnitine with a High-Fat and High-Carbohydrate Diet Modulates Liver Transcriptome in Obesity-Resistant DBA/2J Mice

This study examined the effects of the trans-resveratrol (Res) and l-carnitine (l-Car) complex (RC) on mice genetically resistant to obesity. Male DBA/2J mice received low (RCl, 25/300 mg/kg BW) or high (RCh, 50/600 mg/kg BW) doses of the RC for 64 days in a control diet (CD) or a high-fat-high-carbohydrate diet (HFCD). Differential expression (DE) of genes in the liver was analyzed using DNA microarrays. HFCD alone altered 471 genes (1.7%) versus CD. In CD-fed mice, RCl and RCh affected 170 (0.6%) and 321 (1.2%) genes, respectively. In HFCD-fed mice, RCl and RCh affected 109 (0.4%) and 223 (0.8%) genes. Opposite DE changes between HFCD and RC + HFCD occurred in immune recognition and fat-storage genes (Ccl24, Fabp7, Cd74, H2-Ab1, Srebf1, etc.). Uniform responses to HFCD and RC + CD were seen in Ppard, Irs-1, Tsku, Cyp26b1, Il1r1, Onecut1, Per1, Nlrd2, Rgs16, Grem2, Klf9, and Lpin1. RC effects were consistent with liver morphology. Key RC-targeted pathways included retinoid metabolism, PPAR signaling, and antigen presentation. In HFCD-fed mice, additional pathways were steroid biosynthesis, oxylipin metabolism, and Jak-STAT signaling. DBA/2J mice may exhibit an innate compensatory response involving PPAR signaling, Srebf1, and Socs2, and the contribution of polymorphisms in these genes merits separate investigation in future studies of obesity resistance.