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Adaptation of Intestinal and Bile Acid Physiology Accompany the Metabolic Benefits Following Ileal Interposition in the Rat

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Abstract

Purpose

Ileal interposition recapitulates many of the metabolic improvements similar to Roux-en-Y gastric bypass. We aimed to determine whether the metabolic improvements seen following ileal interposition were conferred solely by the interposed segment by examining changes in neighboring intestinal segments as well as the composition of the bile acid pool.

Materials and Methods

Adult male rats were treated with either sham or ileal interposition surgeries. Glucose tolerance tests, body composition analysis, polymer chain reaction, enzyme-linked immunosorbent assay, and mass spectrometry were done after the surgeries.

Results

This study showed that ileal interposition improved glucose tolerance and enhanced both fasting and glucose-stimulated GLP-1 secretion in diabetic rats. Total bile acid pool was similar between groups but the composition favored glycine-conjugation in rats with ileal interposition. Insulin secretion was highly correlated with the 12-alpha-hydroxylase index of activity. The interposed ileum exhibited an increase in mRNA for preproglucagon and peptide YY; however, the bile acid transporter, apical sodium bile acid transporter, was dramatically reduced compared to sham rats. The interposed segment becomes jejunized in its new location as indicated by an increase in Glut2 and Pepck mRNA, genes predominantly synthesized within the jejunum.

Conclusion

Ileal relocation alone can significantly alter the bile acid pool to favor a more insulin-sensitive metabolism in association with intestinal wide alterations in mRNA for a variety of genes. Ileal interposition may confer metabolic improvement via both the interposed segment and the associated intestinal changes in all segments of the intestine, including the colon.

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Acknowledgements

The present study was supported by funds to Dr. Strader from NIDDK–Challenge Grant 1RC1DK086999-01. A grant (No. 42903) for Ping Zhao from the University of North Alabama College of Arts and Sciences also contributes to the project.

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Authors and Affiliations

  1. Department of Physiology, Southern Illinois University School of Medicine, Carbondale, IL, 62901, USA

    Ping Zhao, Donna Wendt, Sean Z. Goodin, Shwetha Ravichandran & April D. Strader

  2. Department of Biology, University of North Alabama, 1 Harrison Plaza, Florence, AL, 35632, USA

    Ping Zhao

  3. Endocrine, Cardio Metabolic Disease DHT, Eli Lilly and Company, Indianapolis, IN, 46285, USA

    Tara E. Chouinard

Authors
  1. Ping Zhao
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  2. Donna Wendt
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  3. Sean Z. Goodin
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  4. Shwetha Ravichandran
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  5. Tara E. Chouinard
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  6. April D. Strader
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Corresponding author

Correspondence to Ping Zhao.

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Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The welfare of animals used for research has been respected. All applicable institutional and/or national guidelines for the care and use of animals were followed. All animal procedures were approved by the Institutional Animal Care and Use Committee of Southern Illinois University-Carbondale.

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Electronic supplementary material

Supplementary figure 1

Homeostasis model assessment for insulin resistance (HOMA-IR) was calculated using the HOMA formula: HOMA-IR = Fasting insulin (mU/L) × plasma glucose (mg/dL) ÷ 405. The HOMA-IR result correlated with Hyperinsulinemic-euglycemic clamp (r = 0.88) [18]. The insulin resistance in diabetic Long-Evans rats after IT surgery was significantly reduced as compared to sham-operated rats (Student’s t-test; *p < 0.05). (GIF 11 kb)

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Supplementary figure 2

Liver bile-related gene expression in non-diabetic rats following ileal interposition or sham surgery. A number of genes related to bile acid synthesis and signaling were measured within the livers of non-diabetic rats three months following surgery. Although none of the genes were significant at the level of p < 0.05, a few genes approached significance. Interestingly, Fxr exhibited a decrease following ileal interposition (p = 0.05). Sample size was n = 7–9 rats for gene expression analysis. (GIF 20 kb)

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Zhao, P., Wendt, D., Goodin, S.Z. et al. Adaptation of Intestinal and Bile Acid Physiology Accompany the Metabolic Benefits Following Ileal Interposition in the Rat. OBES SURG 28, 725–734 (2018). https://doi.org/10.1007/s11695-017-2886-0

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  • DOI: https://doi.org/10.1007/s11695-017-2886-0

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