Transcriptomic and microRNA analyses of gene networks regulated by eicosapentaenoic acid in brown adipose tissue of diet-induced obese mice

Author(s)/Creator(s)

Latha RamalingamFollow

ORCID

Latha Ramalingam: 0000-0002-4856-7327

Document Type

Article

Date

12-2018

Keywords

Brown adipose tissue, MicroRNA, Obesity, Omega 3 fatty acids, RNA sequencing

Disciplines

Nutrition

Description/Abstract

Brown adipose tissue (BAT) dissipates chemical energy as heat via thermogenesis and protects against obesity by increasing energy expenditure. However, regulation of BAT by dietary factors remains largely unexplored at the mechanistic level. We investigated the effect of eicosapentaenoic acid (EPA) on BAT metabolism. Male C57BL/6J (B6) mice were fed either a high-fat diet (HF, 45% kcal fat) or HF diet supplemented with EPA (HF-EPA, 6.75% kcal EPA) for 11 weeks. RNA sequencing (RNA-Seq) and microRNA (miRNA) profiling were performed on RNA from BAT using Illumina HiSeq and Illumina Genome Analyzer NextSeq, respectively. We conducted pathway analyses using ingenuity pathway analysis software (IPA®) and validated some genes and miRNAs using qPCR. We identified 479 genes that were differentially expressed (2-fold change, n = 3, P ≤ 0.05) in BAT from HF compared to HF-EPA. Genes negatively correlated with thermogenesis such as hypoxia inducible factor 1 alpha subunit inhibitor (Hif1an), were downregulated by EPA. Pathways related to thermogenesis such as peroxisome proliferator-activated receptor (PPAR) were upregulated by EPA while pathways associated with obesity and inflammation such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were downregulated by EPA. MiRNA profiling identified nine and six miRNAs that were upregulated and downregulated by EPA, respectively (log2 fold change > 1.25, n = 3, P ≤ 0.05). Key regulatory miRNAs which were involved in thermogenesis, such as miR-455-3p and miR-129-5p were validated using qPCR. In conclusion, the depth of transcriptomic and miRNA profiling revealed novel mRNA-miRNA interaction networks in BAT which are involved in thermogenesis, and regulated by EPA.

Recommended Citation

Pahlavani M, Wijayatunga NN, Kalupahana NS, Ramalingam L, Gunaratne PH, Coarfa C, Rajapakshe K, Kottapalli P, Moustaid-Moussa N. Transcriptomic and microRNA analyses of gene networks regulated by eicosapentaenoic acid in brown adipose tissue of diet-induced obese mice. Biochim Biophys Acta Mol Cell Biol Lipids. 2018 Dec;1863(12):1523-1531. doi: 10.1016/j.bbalip.2018.09.004. Epub 2018 Sep 25. PMID: 30261280; PMCID: PMC6298436.

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.