Skip to main content
SpringerLink
Log in

Dynamic Adaptive Changes of the Ileum Transposed to the Proximal Small Intestine in Rats

  • Original Contributions
  • Published:
Obesity Surgery Aims and scope Submit manuscript

Abstract

Background

Ileal transposition (IT) is an experimental surgery to investigate the role of the distal ileum in Roux-en-Y gastric bypass (RYGB) surgery. To systematically investigate the dynamic adaptation process of the ileum after IT, we performed transcriptome analyses of the transposed ileum compared with the ileum in situ at different postoperative time points.

Methods

Sprague-Dawley rats fed a chow diet underwent IT or sham surgery. One and 4 weeks after IT or sham surgery, total RNA was extracted from the ileal tissue and subjected to transcriptome analyses using microarray.

Results

Principal component analysis showed that the difference between weeks 1 and 4 was the largest, and the differences between the IT and sham groups were larger in week 4 than in week 1. We identified 1792 differentially expressed genes (DEGs) between IT and sham ileal tissues, including 659 and 1133 DEGs in weeks 1 and 4, respectively. Interestingly, only 45 and 24 DEGs were commonly up- or downregulated in weeks 1 and 4, indicating a marked transition during the adaptation process. Functional enrichment and network analyses showed that structural adaptation predominantly occurred in week 1, while metabolic and immune adaptations predominantly occurred in week 4. These analyses further revealed potential components that modulate structural adaptation (e.g., extracellular matrix) in week 1 and metabolic (e.g., glucose transporter) and immune (e.g., Th17 cells) adaptations in week 4.

Conclusions

The transposed distal ileum underwent dynamic adaptation processes that may help explain the metabolic changes after RYGB.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Rubino F, Nathan DM, Eckel RH, Schauer PR, Alberti KG, Zimmet PZ, del Prato S, Ji L, Sadikot SM, Herman WH, Amiel SA, Kaplan LM, Taroncher-Oldenburg G, Cummings DE, Delegates of the 2nd Diabetes Surgery Summit Metabolic surgery in the treatment algorithm for type 2 diabetes: a joint statement by international diabetes organizations. Diabetes Care 2016;39(6):861–877. PubMed PMID: 27222544

    Article  CAS  Google Scholar 

  2. Oh TJ, Ahn CH, Cho YM. Contribution of the distal small intestine to metabolic improvement after bariatric/metabolic surgery: lessons from ileal transposition surgery. J Diabetes Investig. 2016;7(Suppl 1):94–101.

    Article  CAS  Google Scholar 

  3. Dirksen C, Jorgensen NB, Bojsen-Moller KN, et al. Mechanisms of improved glycaemic control after Roux-en-Y gastric bypass. Diabetologia. 2012;55(7):1890–901.

    Article  CAS  Google Scholar 

  4. Seeley RJ, Chambers AP, Sandoval DA. The role of gut adaptation in the potent effects of multiple bariatric surgeries on obesity and diabetes. Cell Metab. 2015;21(3):369–78.

    Article  CAS  Google Scholar 

  5. Kohli R, Kirby M, Setchell KD, et al. Intestinal adaptation after ileal interposition surgery increases bile acid recycling and protects against obesity-related comorbidities. Am J Physiol Gastrointest Liver Physiol. 2010;299(3):G652–60.

    Article  CAS  Google Scholar 

  6. Oh TJ, Lee HJ, Cho YM. Ileal transposition decreases plasma lipopolysaccharide levels in association with increased L cell secretion in non-obese non-diabetic rats. Obes Surg. 2016;26(6):1287–95.

    Article  Google Scholar 

  7. Strader AD, Vahl TP, Jandacek RJ, et al. Weight loss through ileal transposition is accompanied by increased ileal hormone secretion and synthesis in rats. Am J Physiol Endocrinol Metab. 2005;288(2):E447–53.

    Article  CAS  Google Scholar 

  8. Mencarelli A, Renga B, D’Amore C, et al. Dissociation of intestinal and hepatic activities of FXR and LXRalpha supports metabolic effects of terminal ileum interposition in rodents. Diabetes. 2013;62(10):3384–93.

    Article  CAS  Google Scholar 

  9. Huang d W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4(1):44–57.

    Article  CAS  Google Scholar 

  10. Schuppan D, Riecken EO. Molecules of the extracellular matrix: potential role of collagens and glycoproteins in intestinal adaptation. Digestion. 1990;46(Suppl 2):2–11.

    Article  CAS  Google Scholar 

  11. O’Connor TP, Lam MM, Diamond J. Magnitude of functional adaptation after intestinal resection. Am J Phys. 1999;276(5 Pt 2):R1265–75.

    Google Scholar 

  12. Madsbad S, Dirksen C, Holst JJ. Mechanisms of changes in glucose metabolism and bodyweight after bariatric surgery. Lancet Diabetes Endocrinol. 2014;2(2):152–64.

    Article  CAS  Google Scholar 

  13. Cox AJ, West NP, Cripps AW. Obesity, inflammation, and the gut microbiota. Lancet Diabetes Endocrinol. 2015;3(3):207–15.

    Article  CAS  Google Scholar 

  14. Blaschitz C, Raffatellu M. Th17 cytokines and the gut mucosal barrier. J Clin Immunol. 2010;30(2):196–203.

    Article  CAS  Google Scholar 

  15. Ivanov II, Frutos Rde L, Manel N, et al. Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe. 2008;4(4):337–49.

    Article  CAS  Google Scholar 

  16. Gaboriau-Routhiau V, Rakotobe S, Lecuyer E, et al. The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity. 2009;31(4):677–89.

    Article  CAS  Google Scholar 

  17. Hong CP, Park A, Yang BG, et al. Gut-specific delivery of T-helper 17 cells reduces obesity and insulin resistance in mice. Gastroenterology. 2017;152(8):1998–2010.

    Article  CAS  Google Scholar 

  18. Yiu JH, Dorweiler B, Woo CW. Interaction between gut microbiota and toll-like receptor: from immunity to metabolism. J Mol Med (Berl). 2017;95(1):13–20.

    Article  CAS  Google Scholar 

  19. Hormann N, Brandao I, Jackel S, et al. Gut microbial colonization orchestrates TLR2 expression, signaling and epithelial proliferation in the small intestinal mucosa. PLoS One. 2014;9(11):e113080.

    Article  Google Scholar 

  20. Tremaroli V, Karlsson F, Werling M, et al. Roux-en-Y gastric bypass and vertical banded gastroplasty induce long-term changes on the human gut microbiome contributing to fat mass regulation. Cell Metab. 2015;22(2):228–38.

    Article  CAS  Google Scholar 

  21. Kellett GL, Helliwell PA. The diffusive component of intestinal glucose absorption is mediated by the glucose-induced recruitment of GLUT2 to the brush-border membrane. Biochem J. 2000;350(Pt 1):155–62.

    Article  CAS  Google Scholar 

  22. Cani PD, Holst JJ, Drucker DJ, et al. GLUT2 and the incretin receptors are involved in glucose-induced incretin secretion. Mol Cell Endocrinol. 2007;276(1–2):18–23.

    Article  CAS  Google Scholar 

  23. Mace OJ, Schindler M, Patel S. The regulation of K- and L-cell activity by GLUT2 and the calcium-sensing receptor CasR in rat small intestine. J Physiol. 2012;590(12):2917–36.

    Article  CAS  Google Scholar 

  24. Saeidi N, Meoli L, Nestoridi E, et al. Reprogramming of intestinal glucose metabolism and glycemic control in rats after gastric bypass. Science. 2013;341(6144):406–10.

    Article  CAS  Google Scholar 

Download references

Funding

This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI14C1277); a grant from the Institute for Basic Science (IBS-R013-A1); and a grant from KBRI basic research program through the Korea Brain Research Institute funded by the Ministry of Science and ICT (20180043).

Author information

Author notes

  1. Chang Ho Ahn and Sehyun Chae contributed equally to this work.

Authors and Affiliations

  1. Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea

    Chang Ho Ahn, Tae Jung Oh & Young Min Cho

  2. Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea

    Chang Ho Ahn & Young Min Cho

  3. Center for Plant Aging Research, Institute for Basic Science, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Republic of Korea

    Sehyun Chae & Daehee Hwang

  4. Korea Brain Research Institute (KBRI), Daegu, Republic of Korea

    Sehyun Chae

  5. Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea

    Tae Jung Oh

  6. Department of Biological Sciences, Seoul National University, Seoul, 08826, Republic of Korea

    Daehee Hwang

Authors
  1. Chang Ho Ahn
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sehyun Chae
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tae Jung Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Daehee Hwang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Young Min Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Daehee Hwang or Young Min Cho.

Ethics declarations

Competing Interests

The authors declare that they have no conflicts of interest.

Statement of Animal Rights/Ethical Approval

All animal experiments were approved by the Institutional Animal Care and Use Committee of Seoul National University Hospital (approval no. 13-0273).

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic Supplementary Material

Supplementary Method

. Detailed protocol of Histology and immunohistochemistry, analysis of gene expression data, and network analysis. (DOCX 30 kb)

Supplementary Figure S1

Correlation between the key gene expression levels measured by microarray and RT-PCR. Data are presented as the log2-fold-change compared to the mean value of the control group (sham group). Linear regression analysis was performed to calculate Pearson’s correlation coefficient and the P value. (PNG 201 kb)

High resolution image (TIF 9417 kb)

Supplementary Table S1.

Primers for qRT-PCR analysis of key genes. (DOCX 12 kb)

Supplementary Table S2.

List of differentially expressed genes (DEGs). For each DEG, the Entrez ID, gene symbol (HUGO), and gene description are shown together with the log2-fold-change and false discovery rate from the comparisons of the IT and sham groups in weeks 1 and 4 after surgery. Additionally, the cluster (C1-8) to which the DEG belongs and whether the DEG showed up-regulation (1), down-regulation (-1), or no change in the comparisons are noted. (XLSX 206 kb)

Supplementary Table S3.

GOBPs enriched by genes in C1-8. For each GOBP, the description of the GOBP (GOTERM_BP) is shown together with the number of DEGs (Count) involved in the GOBP in each cluster and the enrichment P-value (P-value) for the GOBP. The GOBPs shown in Figure 2B are denoted by a red background. (XLSX 92 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ahn, C.H., Chae, S., Oh, T.J. et al. Dynamic Adaptive Changes of the Ileum Transposed to the Proximal Small Intestine in Rats. OBES SURG 29, 2399–2408 (2019). https://doi.org/10.1007/s11695-019-03858-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11695-019-03858-9

Keywords

Search

Navigation