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  • Bariatric and Metabolic Surgery Original Article
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Ileal transposition surgery produces ileal length-dependent changes in food intake, body weight, gut hormones and glucose metabolism in rats

International Journal of Obesity volume 38, pages 379–387 (2014)Cite this article

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Abstract

Background:

Enhanced stimulation of the lower gut is hypothesized to play a key role in the weight loss and resolution of diabetes following bariatric surgeries. Ileal transposition (IT) permits study of the effects of direct lower gut stimulation on body weight, glucose homeostasis and other metabolic adaptations without the confounds of gastric restriction or foregut exclusion. However, the underlying mechanisms and the length of the ileum sufficient to produce metabolic benefits following IT surgery remain largely unknown.

Objective:

To determine the effects of transposing varying lengths of the ileum to upper jejunum on food intake, body weight, glucose tolerance and lower gut hormones, and the expression of key markers of glucose and lipid metabolism in skeletal muscle and adipose tissue in rats.

Methods:

Adult male Sprague–Dawley rats (n=9/group) were subjected to IT surgery with translocation of 5, 10 or 20 cm of the ileal segment to proximal jejunum or sham manipulations. Daily food intake and body weight were recorded, and an intraperitoneal glucose tolerance test was performed. Blood samples were assayed for hormones and tissue samples for mRNA (RT–qPCR) and/or protein abundance (immunoblotting) of regulatory metabolic markers.

Results:

We demonstrate that IT surgery exerts ileal length-dependent effects on multiple parameters including: (1) decreased food intake and weight gain, (2) improved glucose tolerance, (3) increased tissue expression and plasma concentrations of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), and decreased leptin concentrations and (4) upregulation of key markers of glucose metabolism (glucose transporter-4 (GLUT-4), insulin receptor substrate 1 (IRS-1), adenosine monophosphate-activated protein kinase (AMPK), hexokinase (HK) and phosphofructokinase (PFK)) together with a downregulation of lipogenic markers (fatty acid synthase (FAS)) in muscle and adipose tissue.

Conclusions:

Together, our data demonstrate that the reduction in food intake and weight gain, increase in lower gut hormones, glycemic improvements and associated changes in tissue metabolic markers following IT surgery are dependent on the length of the transposed ileum.

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Acknowledgements

This work was supported by a Grant-in-Aid from the Heart and Stroke Foundation of Canada, Canada Foundation for Innovation, and the Koopmans Memorial Research Fund to PKC. AR was supported by studentships from the Natural Sciences and Engineering Research Council of Canada and Faculty of Veterinary Medicine. SN was supported by a graduate scholarship from the Faculty of Veterinary Medicine and a Queen Elizabeth II Graduate Scholarship. We appreciate the help of Imran Shah, David Min and Adel Pezeshki.

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Authors and Affiliations

  1. Department of Production Animal Health, Faculty of Veterinary Medicine, Calgary, Alberta, Canada

    A R Ramzy, S Nausheen & P K Chelikani

  2. Gastrointestinal Research Group, Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada

    P K Chelikani

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  1. A R Ramzy
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Correspondence to P K Chelikani.

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Author contributions

SN and PKC designed the study, AR and SN performed experiments, AR, SN and PKC conducted the tissue analyses, AR and PKC were responsible for the analysis and interpretation of data, PKC obtained funding, AR drafted the manuscript, AR, SN, PKC undertook the critical revision of the manuscript for important intellectual content and AR, SN and PKC approved the final version of the manuscript.

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Ramzy, A., Nausheen, S. & Chelikani, P. Ileal transposition surgery produces ileal length-dependent changes in food intake, body weight, gut hormones and glucose metabolism in rats. Int J Obes 38, 379–387 (2014). https://doi.org/10.1038/ijo.2013.201

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