Characterization of genome-wide transcriptional changes in liver and adipose tissues of ZDF (fa/fa) rats fed R-α-lipoic acid by next-generation sequencing

Anjeza Pashaj, Xiaohua Yi, Mengna Xia, Stephanie Canny, Jean-Jack M Riethoven, Regis F Moreau

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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-α-lipoic acid (LA). Nine-week-old male Zucker diabetic fatty (fa/fa) rats were fed a chow diet supplemented with 3 g LA per kg diet or pair fed for 2 wk. At the end of the trial, high-quality RNA was extracted from the liver and epididymal fat and subjected to transcriptome analysis by RNA-Seq technology. Results showed a substantially higher number of differentially expressed genes [DEG, false discovery rate adjusted P ≤ 0.05 and absolute log2 (fold change) ≥ 1] in the 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, interferonrelated genes involved in defense against microorganisms 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, Elovl6, Acly, Gpam, and Aacs) and concomitant upregulation of short-, medium-, and longchain 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.

Original languageEnglish (US)
Pages (from-to)1136-1143
Number of pages8
JournalPhysiological genomics
Volume45
Issue number23
DOIs
StatePublished - Dec 1 2013

Fingerprint

Thioctic Acid
Adipose Tissue
Genome
Liver
Gene Ontology
Genes
Fats
Lipid Metabolism
RNA
Diet
Lipids
Gene Regulatory Networks
Adiposity
Gene Expression Profiling
Dietary Supplements
Carboxylic Acids
Innate Immunity
Triglycerides
Up-Regulation
Fatty Acids

Keywords

  • Dyslipidemia
  • Nonalcoholic fatty liver disease
  • Nutritional genomics

ASJC Scopus subject areas

  • Physiology
  • Genetics

Cite this

Characterization of genome-wide transcriptional changes in liver and adipose tissues of ZDF (fa/fa) rats fed R-α-lipoic acid by next-generation sequencing. / Pashaj, Anjeza; Yi, Xiaohua; Xia, Mengna; Canny, Stephanie; Riethoven, Jean-Jack M; Moreau, Regis F.

In: Physiological genomics, Vol. 45, No. 23, 01.12.2013, p. 1136-1143.

Research output: Contribution to journalArticle

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abstract = "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-α-lipoic acid (LA). Nine-week-old male Zucker diabetic fatty (fa/fa) rats were fed a chow diet supplemented with 3 g LA per kg diet or pair fed for 2 wk. At the end of the trial, high-quality RNA was extracted from the liver and epididymal fat and subjected to transcriptome analysis by RNA-Seq technology. Results showed a substantially higher number of differentially expressed genes [DEG, false discovery rate adjusted P ≤ 0.05 and absolute log2 (fold change) ≥ 1] in the 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, interferonrelated genes involved in defense against microorganisms 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, Elovl6, Acly, Gpam, and Aacs) and concomitant upregulation of short-, medium-, and longchain 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.",
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