High-Fat Diet Alters the Retinal Pigment Epithelium and Choroidal Transcriptome in the Absence of Gut Microbiota
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals and Diets
2.2. Sterility Monitoring
2.3. RNA Extraction
2.4. RNA Sequencing
2.5. Statistical Analysis
3. Results
3.1. High-Fat Diet Is Associated with Changes in the Rpe/Choroid Transcriptome
3.2. High-Fat Diet Upregulates Multiple Biological Processes and Genes Related to Inflammation and Angiogenesis
4. Discussion
4.1. High-Fat Diet Affects Gene Expression in Angiogenic Pathways in Germ-Free Mice
4.2. High-Fat Diet Alters Gene Expression Involved in Inflammatory and Immune Response Pathways in Germ-Free Mice
4.3. High-Fat Diet Affects Gene Expression Involved in the Complement System
4.4. Additional Genes and Pathways Are Differentially Represented by High-Fat Diet in Germ-Free Mice
5. Conclusions and Limitations
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Gene | LogFC | Adjusted p-Value | Protein |
---|---|---|---|
Cd244a | 6.27 | 1.62 × 10−3 | Natural Killer Cell Receptor 2B4 |
Ripply1 | 5.52 | 9.98 × 10−3 | Ripply Transcriptional Repressor 1 |
Lilrb4a | 5.28 | 4.81 × 10−2 | Leukocyte Immunoglobulin-Like Receptor Subfamily B member 4 |
Fcer1a | 5.26 | 2.85 × 10−2 | Fc Epsilon Receptor Ia |
Dnajc22 | 5.24 | 1.44 × 10−2 | DnaJ Heat Shock Protein Family (Hsp40) Member C22 |
Alkal2 | 5.11 | 3.11 × 10−2 | ALK And LTK Ligand 2 |
Ncr1 | 5.04 | 1.16 × 10−2 | Natural Cytotoxicity Triggering Receptor 1 |
Ccl19 | 4.94 | 7.60 × 10−3 | C-C Motif Chemokine Ligand 19 |
Slc38a11 | 4.81 | 3.85 × 10−2 | Solute Carrier Family 38 Member 11 |
Ces2e | 4.71 | 4.62 × 10−2 | Pyrethroid Hydrolase Ces2e |
Lpar3 | 4.66 | 1.73 × 10−2 | Lysophosphatidic Acid Receptor 3 |
Sele | 4.62 | 4.49 × 10−2 | Selectin E |
Sirpb1a | 4.61 | 9.02 × 10−3 | Signal-Regulatory Protein Beta 1A |
Efhb | 4.57 | 1.33 × 10−2 | EF-Hand Domain-Containing Family Member B |
Pgpep1l | 4.56 | 2.15 × 10−2 | Pyroglutamyl-Peptidase 1-Like Protein |
Tnfrsf13b | 4.54 | 2.94 × 10−2 | Tumor Necrosis Factor Receptor Superfamily Member 13B |
Il12b | 4.49 | 2.65 × 10−2 | Interleukin-12 Subunit Beta |
Tmem232 | 4.46 | 2.53 × 10−2 | Transmembrane Protein 232 |
Trbc1 | 4.41 | 1.51 × 10−2 | T Cell Receptor Beta Constant 1 |
Slc4a1 | 4.34 | 3.36 × 10−2 | Solute Carrier Family 4 Member 1 |
Olfr574 | 4.34 | 1.60 × 10−2 | Olfactory Receptor Family 51 Subfamily T Member 1 |
Xlr | 4.28 | 5.51 × 10−3 | X-Linked Lymphocyte-Regulated Protein PM1 |
Gpr141 | 4.25 | 4.73 × 10−2 | G Protein-Coupled Receptor 141 |
Cnr2 | 4.25 | 3.48 × 10−2 | Cannabinoid Receptor 2 |
Mael | 4.23 | 4.08 × 10−2 | Maelstrom Spermatogenic Transposon Silencer |
Lao1 | 4.22 | 4.06 × 10−2 | Amine Oxidase |
Mcoln2 | 4.16 | 1.72 × 10−2 | Mucolipin TRP Cation Channel 2 |
Ccl22 | 4.16 | 3.77 × 10−2 | C-C Motif Chemokine Ligand 22 |
Rnase1 | 4.11 | 2.66 × 10−2 | Ribonuclease A Family Member 1, Pancreatic |
Ptgs2os | 4.11 | 3.37 × 10−2 | Prostaglandin-Endoperoxide Synthase 2, Opposite Strand |
Biological Processes | p-Value | Adjusted p-Value | Gene Ratio | Genes |
---|---|---|---|---|
Melanocyte differentiation | 1.79 × 10−7 | 9.49 × 10−5 | 0.35 | Edn3, Ednrb, Mitf, Mlph, Rab27a, Slc24a5, Sox10, and Tyrp1 |
Angiogenesis | 2.08 × 10−13 | 5.51 × 10−10 | 0.13 | Ackr3, Angpt1, Angpt2, Angptl2, Apold1, Calcrl, Cfh, Clic4, Col18a1, Col8a1, Col8a2, Cxcr3, Cyp1b1, Ecscr, Ephb4, Esm1, Fap, Fzd8, Htatip2, Mcam, Nrp2, Pik3r6, Plxnd1, Ptgs2, Ptprb, Rapgef3, Rhoj, Rspo3, Tbx4, Tek, Tgfbr3, Tie1, Tnfaip2, and Vegfc |
Cell surface receptor signaling pathway | 1.50 × 10−9 | 1.50 × 10−6 | 0.13 | Adgra3, Adgrf5, Adgrg6, Calcrl, Cd22, Cd86, Cxcr3, Cysltr1, Edn3, Fcer1a, Fzd2, Fzd4, Fzd7, Fzd8, Gpr157, Il12b, Itgal, Itpkb, Npr1, Osmr, Ostn, Pth1r, Tnfrsf1b, and Tshr |
Positive regulation of angiogenesis | 5.68 × 10−7 | 2.15 × 10−4 | 0.12 | Angpt2, Brca1, Chil1, Cxcr3, Cybb, Cyp1b1, Cysltr1, Ets1, Itgb3, Itgb8, Pik3r6, Ptgis, Rapgef3, Tek, Tgfbr2, Thbs1, Tie1, and Vegfc |
Inflammatory response | 1.14 × 10−9 | 1.50 × 10−6 | 0.10 | Agtr1a, Axl, Bmp2, Bmp6, Ccl19, Ccl22, Ccl4, Cfh, Chil1, Cnr2, Csf1r, Cxcl10, Cxcr3, Cyba, Cybb, Cysltr1, Gbp5, Il25, Lilrb4a, Lipa, Ly86, P2rx7, Pla2g2e, Prkcq, Ptgs1, Ptgs2, Rarres2, Sele, Selp, Slc11a1, Thbs1, Themis2, Tlr13, and Tnfrsf1b |
Response to bacterium | 1.29 × 10−6 | 3.56 × 10−4 | 0.09 | Adamts9, Bank1, Bmp2, Cxcl10, Fkbp5, Gbp5, Gpc3, Gzma, Ifi211, Ifit3, Iigp1, Lrat, Ms4a1, Myo1f, Naaladl2, Nexn, Ociad2, P2rx7, Rnase1, Serpina3f, Serpinb9, Slc11a1, Tgtp1, and Trf |
Immune response | 8.75 × 10−7 | 2.90 × 10−4 | 0.08 | Ackr3, Azgp1, B2m, Bmp6, Ccl19, Ccl22, Ccl4, Cd28, Cd86, Cfh, Colec12, Ctsk, Ctss, Cxcl10, Cxcl12, Cxcr3, Endou, Enpp2, H2-Ab1, H2-Eb1, H2-M3, Itgb8, Ly86, Serpinb9, Tgfbr3, Tgtp1, Tnfrsf1b, Tnfsf10, Tnfsf14, Vav1 |
Cell adhesion | 1.48 × 10−8 | 9.80 × 10−6 | 0.08 | Ackr3, Azgp1, Cd22, Cd33, Cd84, Cldn1, Cldn2, Cntnap4, Col12a1, Col18a1, Col8a1, Col8a2, Cyp1b1, Dpp4, Ephb4, Fap, Fblim1, Fbln5, Gpnmb, Hpse, Icam2, Itga9, Itgal, Itgb3, Itgb8, Jcad, Kitl, Lgals3bp, Ly9, Mcam, Mybpc2, Nid2, Pcdh12, Plpp3, Sele, Sell, Selp, Siglecf, Spp1, Svep1, Thbs1, Vcam1, and Vwf |
Positive regulation of cell population proliferation | 1.98 × 10−7 | 9.49 × 10−5 | 0.07 | Adora2b, Agtr1a, Aldh1a2, Bambi, Calcrl, Cd38, Cdk2, Clec7a, Col18a1, Csf1r, Cxcl10, Cxcl12, Cxcr3, Dpp4, Edn3, Ednra, Ednrb, Enpp2, Esm1, Ets1, Fgf7, Gab2, Gcnt2, Gli1, Kitl, Lrp5, Nog, Ntn1, Osmr, Pax3, Pdgfc, Pdgfd, Ptgs2, Pth1r, S100b, Stox1, Tgfbr3, Thbs1, Tshr, and Vegfc |
Multicellular organism development | 1.21 × 10−6 | 3.56 × 10−4 | 0.06 | Ackr3, Angpt1, Angpt2, Ano1, Axl, B2m, Bmp2, Bmp6, Cdh19, Csf1r, Ecscr, Eda2r, Ephb4, Eya1, Eya2, Fhl1, Foxd1, Foxd3, Fst, Fzd2, Fzd4, Fzd7, Fzd8, Gli1, Gpr157, Gsx2, Htatip2, Krt8, Lbx1, Lrp5, Mael, Mertk, Met, Mgp, Mitf, Nog, Nrp2, Ostn, Pax3, Pdgfc, Pdgfd, Pitx2, Plpp3, Plxnd1, Ripply1, Sema3b, Sema3c, Sema6d, Serpine2, Sfrp5, Shisa2, Smoc1, Sox6, Stpg4, Tbx4, Tek, Tie1, Tmem88, Tnfaip2, Vegfc, and Wipf3 |
Molecular Pathways | p-Value | Adjusted p-Value | Gene Ratio | Genes |
---|---|---|---|---|
Hemoglobin binding | 2.43 × 10−5 | 3.96 × 10−3 | 0.57 | Hbb-bs, Hbb-bt, Lrp2, Slc4a1 |
Sialic acid binding | 2.30 × 10−5 | 3.96 × 10−3 | 0.38 | Cd22, Cd33, Sele, Selp, Siglecf |
Extracellular matrix binding | 2.09 × 10−5 | 3.96 × 10−3 | 0.23 | Adamts15, Clec14a, Dcn, Itgb3, Smoc1, Spp1, and Thbs1 |
Fibronectin binding | 2.64 × 10−5 | 3.96 × 10−3 | 0.23 | Ctsk, Ctss, Fbln1, Igfbp3, Igfbp5, Itgb3, Thbs1 |
Integrin binding | 2.81 × 10−7 | 2.12 × 10−4 | 0.13 | Cxcl12, Esm1, Fap, Fbln1, Fbln5, Fbn1, Gpnmb, Icam2, Itgb3, Itgb8, Lcp1, Lilrb4a, Plpp3, Spp1, Thbs1, Vcam1, and Vwf |
Extracellular matrix structural constituent | 5.40 × 10−5 | 4.08 × 10−3 | 0.11 | Col10a1, Col18a1, Col8a1, Col8a2, Col9a3, Fbln1, Fbn1, Fbn2, Matn2, Nid2, Ntn1, Thbs1, Vwf |
Signaling receptor activity | 4.79 × 10−6 | 1.21 × 10−3 | 0.10 | Cd48, Colec12, Cxcr3, Eda2r, Fzd4, Itgb8, Klrk1, Lrp2, Mrc2, P2rx7, Paqr6, Stra6, Tek, Tgfbr2, Tlr13, Tnfrsf19, Trem2, and Tshr |
Carbohydrate binding | 2.04 × 10−6 | 7.73 × 10−4 | 0.10 | Agl, C4b, Cd22, Cd33, Clec12a, Clec14a, Clec1a, Clec4a2, Clec4d, Clec4n, Colec12, Galm, Galnt6, Klrk1, Man2a1, Mrc2, Sele, Sell, Selp, Siglecf |
Heparin binding | 4.12 × 10−5 | 3.96 × 10−3 | 0.10 | Adamts1, Adamts15, Apoe, Cfh, Cxcl10, Fbn1, Fgf7, Gpnmb, Nrp2, Rspo3, Selp, Serpine2, Smoc1, Tgfbr3, and Thbs1 |
Protein homodimerization activity | 2.24 × 10−5 | 3.96 × 10−3 | 0.06 | Ano1, Ano6, Apoe, Atp2a1, B2m, Cat, Csf1r, Dpp4, Dpyd, Fap, Fbln5, Fzd4, Galm, Gbp3, Gbp5, Gzma, H2-M3, Hnf4a, Impa2, Man2a1, Mgll, Nog, Npr3, Pdgfc, Pitx2, Pon1, Pon3, Ptgs2, Pth1r, Rdh5, S100b, Slc11a1, Slc4a1, St6gal1, Tpd52l1, Trim21, Trim30d, Tyr, Tyrobp, and Tyrp1 |
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Xiao, J.; Xie, B.; Dao, D.; Spedale, M.; D’Souza, M.; Theriault, B.; Hariprasad, S.M.; Sulakhe, D.; Chang, E.B.; Skondra, D. High-Fat Diet Alters the Retinal Pigment Epithelium and Choroidal Transcriptome in the Absence of Gut Microbiota. Cells 2022, 11, 2076. https://doi.org/10.3390/cells11132076
Xiao J, Xie B, Dao D, Spedale M, D’Souza M, Theriault B, Hariprasad SM, Sulakhe D, Chang EB, Skondra D. High-Fat Diet Alters the Retinal Pigment Epithelium and Choroidal Transcriptome in the Absence of Gut Microbiota. Cells. 2022; 11(13):2076. https://doi.org/10.3390/cells11132076
Chicago/Turabian StyleXiao, Jason, Bingqing Xie, David Dao, Melanie Spedale, Mark D’Souza, Betty Theriault, Seenu M. Hariprasad, Dinanath Sulakhe, Eugene B. Chang, and Dimitra Skondra. 2022. "High-Fat Diet Alters the Retinal Pigment Epithelium and Choroidal Transcriptome in the Absence of Gut Microbiota" Cells 11, no. 13: 2076. https://doi.org/10.3390/cells11132076
APA StyleXiao, J., Xie, B., Dao, D., Spedale, M., D’Souza, M., Theriault, B., Hariprasad, S. M., Sulakhe, D., Chang, E. B., & Skondra, D. (2022). High-Fat Diet Alters the Retinal Pigment Epithelium and Choroidal Transcriptome in the Absence of Gut Microbiota. Cells, 11(13), 2076. https://doi.org/10.3390/cells11132076