GSE50424
Characterization of genome-wide transcriptional changes in liver and adipose tissues of ZDF (fa/fa) rats fed R-a-lipoic acid by next-generation sequencing
We report on the characterization of lipogenic tissue transcriptional networks that support physiological responses of obese rats to a lipid-lowering bioactive food compound, R-a-lipoic acid (LA). Nine-week old male ZDF (fa/fa) rats were fed a chow diet supplemented with 3 g LA per kg diet or pair fed for two weeks. At the end of the trial, high-quality RNA was extracted from the liver and epididymal fat and subjected to transcriptome analysis using RNA-Seq technology. Results showed a substantially higher number of differentially expressed genes (DEG, q = 0.05 and absolute log2(fold change) = 1) in liver (110 genes) vs. epididymal fat (10 genes). Most epididymal fat DEG were also differentially expressed in liver and shared directionality of change. Gene Ontology (GO) analysis of these transcripts revealed significant enrichment of GO categories related to immune response, stress response, lipid metabolism, and carboxylic acid metabolic processes. Of interest interferon-related genes involved in defense against microorganism and innate immune response were induced by LA. Lipid metabolism-related transcript changes observed in LA-fed animals included downregulation of lipogenic genes (Pnpla3, Pnpla5, Elov6, Acly, Gpam, and Aacs) and concomitant upregulation of short-, medium- and long-chain fatty acid metabolic processes (Acot1, Acot2, Acsf2, and Crat). Transcriptional changes were accompanied by the lowering of abdominal adiposity and blood triacylglycerol levels. We conclude that LA dietary supplementation induces prominent gene expression changes in liver in support of significant improvement of whole-body lipid status Overall design: For each tissue and feed combination (liver/LA+, liver/LA-, adipose/LA+, and adipose/LA-) the transcriptome was sequenced with 4 biological replicates.