An Integrated Analysis of miRNA and Gene Expression Changes in Response to an Obesogenic Diet to Explore the Impact of Transgenerational Supplementation with Omega 3 Fatty Acids
Abstract
1. Introduction
2. Materials and Methods
2.1. Dietary Intervention and Sample Collection
2.2. Gene Expression and miRNA Analysis
2.2.1. Microarray Gene Expression Analysis
2.2.2. Small RNA Sequencing (Small RNA-Seq) Analysis
2.3. Bioinformatic and Statistical Analysis
2.3.1. Gene Differential Expression between Biological Conditions
2.3.2. Testing Gene Signature Performances with Partial Least-Squares Discriminant Analysis and Hierarchical Clustering
2.3.3. Application of MicroRNA Master Regulator Analysis (MMRA)
- MMRA step1: MiRNA differential expression analysis
- MMRA step2: target genes enrichment analysis
- MMRA step3: network analysis
- MMRA step4: Step-wise Linear Regression (SLR) analysis
2.4. Pathways Analysis
2.4.1. Molecular Pathway Analysis with GeneTrail2
2.4.2. Metabolic Pathways Analysis with MetExplore
2.5. Logical Modeling of Gene Regulatory and Metabolic Networks
2.6. Validation of Gene Expression
3. Results
3.1. Effect of High Fat Diet and Transgenerational Supplementation with EPA in Gene and miRNAs Expression
3.2. MiRNAs Significantly Contribute to the Expression of Phenotype Signature Gene
3.3. Identification of Differentially Regulated Cellular and Signaling Pathways
3.4. Differential Enrichment of Metabolic Pathways in HFepa and HFoleic Groups
3.5. MiRNAs Regulated Genes Involved in the Integration of Insulin Signaling, PPAR Signaling, Glucose Metabolism, and FA Metabolism
3.6. Computational Modeling Predicts that Dynamism in Genes and miRNAs Expression Leads to Specific Cell Metabolic Phenotypes
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Parameter- | Reference | HFoleic | HFepa | ||||||
---|---|---|---|---|---|---|---|---|---|
Body Weight (g) | 26.7 | ± | 0.9 | 36.1 | ± | 1 *** | 33.8 | ± | 2.7 ** |
Fat % | 16 | ± | 1 | 32 | ± | 1 *** | 24 | ± | 3 ** † |
Lean % | 79 | ± | 1 | 64 | ± | 1 *** | 72 | ± | 3 ** †† |
Liver (gram) | 0.87 | ± | 0.04 | 1.11 | ± | 0.04 * | 0.99 | ± | 0.09 |
AUCglucose (a.u.) | 171 | ± | 6 | 207 | ± | 11 * | 196 | ± | 8 |
Glucose (mg/dL) | 195.6 | ± | 13.1 | 274.2 | ± | 13.1 ** | 228.1 | ± | 14.0 † |
Insulin (pg/mL) | 68.6 | ± | 8.3 | 182.8 | ± | 18.8 *** | 109.4 | ± | 25.9 † |
TAG (g/L) | 0.310 | ± | 0.013 | 0.366 | ± | 0.024 | 0.378 | ± | 0.039 |
T Cholesterol (g/L) | 0.926 | ± | 0.034 | 1.116 | ± | 0.050 * | 1.166 | ± | 0.068 * |
Glycerol (µM) | 213.1 | ± | 11.9 | 237.2 | ± | 19.0 | 257.1 | ± | 24.0 |
Nefa (mM) | 0.350 | ± | 0.038 | 0.228 | ± | 0.029 | 0.404 | ± | 0.081 |
Gene | Associated Signature in HFepa | Associated Signature in HFoleic | miRNA Regulation | microRNA Regulation in HFepa | microRNA Regulation in HFoleic |
---|---|---|---|---|---|
Sigmar1 | Down | mmu.miR.32.5p | up | ||
Xpa | Down | Down | mmu.miR.150.5p | down | |
Xpa | Down | Down | mmu.miR.335.3p | up | up |
Xpa | Down | Down | mmu.miR.1948.3p | up | up |
Rai1 | Down | mmu.miR.7052.3p | down | ||
Zfp777 | Down | Down | mmu.miR.335.3p | up | up |
Txn2 | Down | Down | mmu.miR.18a.3p | up | |
Txn2 | Down | Down | mmu.miR.98.3p | down | |
Trpt1 | Down | Down | mmu.miR.148a.3p | up | |
Agpat6 | Down | Down | mmu.miR.195a.3p | down | down |
Leng9 | Down | Down | mmu.miR.7052.3p | down | |
Plekhf1 | up | up | mmu.miR.150.5p | down | |
Plekhf1 | up | up | mmu.miR.335.3p | up | up |
Stard4 | up | up | mmu.miR.32.5p | up | |
Stard4 | up | up | mmu.miR.7052.3p | down | |
Dnajb1 | up | mmu.miR.19a.3p | down | ||
Dnajb1 | up | mmu.miR.7068.3p | down | down | |
Hspb1 | up | up | mmu.miR.128.3p | down | down |
Hspb1 | up | up | mmu.miR.150.5p | down | |
Hspb1 | up | up | mmu.miR.7068.3p | down | down |
Pcp4l1 | up | up | mmu.miR.1948.3p | up | up |
A_55_P2525368 | Down | miRNA regulation not significant | |||
Ptpmt1 | Down | Down | miRNA regulation not significant | ||
Magohb | Down | miRNA regulation not significant | |||
A130022F02Rik | Down | Down | miRNA regulation not significant | ||
Gm13547 | Down | Down | no regulated by a miRNA | ||
Lrrfip1 | Down | Down | no regulated by a miRNA | ||
Rabl3 | Down | Down | no regulated by a miRNA | ||
Kansl1l | up | up | miRNA regulation not significant | ||
P4ha1 | up | miRNA regulation not significant | |||
Inhbb | up | miRNA regulation not significant | |||
Mtss1 | up | up | miRNA regulation not significant | ||
Hyou1 | up | up | miRNA regulation not significant | ||
Gbe1 | up | up | miRNA regulation not significant | ||
Slc5a3 | up | up | miRNA regulation not significant | ||
Ints6 | up | up | miRNA regulation not significant | ||
0610031O16Rik | up | up | no regulated by a miRNA |
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Corral-Jara, K.F.; Cantini, L.; Poupin, N.; Ye, T.; Rigaudière, J.P.; Vincent, S.D.S.; Pinel, A.; Morio, B.; Capel, F. An Integrated Analysis of miRNA and Gene Expression Changes in Response to an Obesogenic Diet to Explore the Impact of Transgenerational Supplementation with Omega 3 Fatty Acids. Nutrients 2020, 12, 3864. https://doi.org/10.3390/nu12123864
Corral-Jara KF, Cantini L, Poupin N, Ye T, Rigaudière JP, Vincent SDS, Pinel A, Morio B, Capel F. An Integrated Analysis of miRNA and Gene Expression Changes in Response to an Obesogenic Diet to Explore the Impact of Transgenerational Supplementation with Omega 3 Fatty Acids. Nutrients. 2020; 12(12):3864. https://doi.org/10.3390/nu12123864
Chicago/Turabian StyleCorral-Jara, Karla Fabiola, Laura Cantini, Nathalie Poupin, Tao Ye, Jean Paul Rigaudière, Sarah De Saint Vincent, Alexandre Pinel, Béatrice Morio, and Frédéric Capel. 2020. "An Integrated Analysis of miRNA and Gene Expression Changes in Response to an Obesogenic Diet to Explore the Impact of Transgenerational Supplementation with Omega 3 Fatty Acids" Nutrients 12, no. 12: 3864. https://doi.org/10.3390/nu12123864
APA StyleCorral-Jara, K. F., Cantini, L., Poupin, N., Ye, T., Rigaudière, J. P., Vincent, S. D. S., Pinel, A., Morio, B., & Capel, F. (2020). An Integrated Analysis of miRNA and Gene Expression Changes in Response to an Obesogenic Diet to Explore the Impact of Transgenerational Supplementation with Omega 3 Fatty Acids. Nutrients, 12(12), 3864. https://doi.org/10.3390/nu12123864