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Intestinal Glucose Absorption Was Reduced by Vertical Sleeve Gastrectomy via Decreased Gastric Leptin Secretion

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Abstract

Background

The unique effects of gastric resection after vertical sleeve gastrectomy (VSG) on type 2 diabetes mellitus remain unclear. This work aimed to investigate the effects of VSG on gastric leptin expression and intestinal glucose absorption in high-fat diet-induced obesity.

Methods

Male C57BL/6J mice were fed a high-fat diet (HFD) to induce obesity. HFD mice were randomized into VSG and sham-operation groups, and the relevant parameters were measured at 8 weeks postoperation.

Results

Higher gastric leptin expression and increased intestinal glucose transport were observed in the HFD mice. Furthermore, VSG reduced gastric leptin expression and the intestinal absorption of alimentary glucose. Both exogenous leptin replenishment during the oral glucose tolerance test (OGTT) and the addition of leptin into the everted isolated jejunum loops in vitro restored the glucose transport capacity in VSG-operated mice, and this effect was abolished when the glucose transporter GLUT2 was blocked with phloretin. Moreover, phloretin almost completely suppressed glucose transport in the HFD mice. Intestinal immunohistochemistry in the obese mice showed increased GLUT2 and diminished sodium glucose co-transporter 1 (SGLT-1) in the apical membrane of enterocytes. Decreased GLUT2 and enhanced SGLT1 were observed following VSG. VSG also reduced the phosphorylation status of protein kinase C isoenzyme β II (PKCβ II) in the jejunum, which was stimulated by the combination of leptin and glucose.

Conclusion

Our data demonstrated that the decreased secretion of gastric leptin in VSG results in a decrease in intestinal glucose absorption via modulation of GLUT2 translocation.

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Funding

This study was supported by National Key Basic Research Program of China (No. 2015CB5540007); National Natural Science Foundation of China (No. 81472740, 81200276, and 81700488); Natural Science Foundation of Hubei Province of China (No. 2014CFA060 and 2015CFB710); Research Fund of Public Welfare in Health Industry, Health and Family Plan Committee of China (No. 201402015); Natural Science Foundation of Huazhong University of Science and Technology (No. 5001530030), and Health and Family Planning Youth Project Foundation of Hubei Province, China (No. WJ2015Q001).

Author information

Authors and Affiliations

  1. Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, China

    Jinpeng Du, Chaojie Hu, Jie Bai, Qingbo Wang, Ning Zhao, Yu Wang, Guobin Wang, Kaixiong Tao, Geng Wang & Zefeng Xia

  2. Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, China

    Miaomiao Peng

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  1. Jinpeng Du
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Corresponding authors

Correspondence to Geng Wang or Zefeng Xia.

Ethics declarations

All animal studies (including the mice euthanasia procedure) were conducted in compliance with the regulations and guidelines of Tongji Medicine College institutional animal care committee.

Conflict of Interest

The authors declare that they have no conflict of interest.

A Statement of Animal Rights/Ethical Approval

All procedures in this study were approved by the Ethics Committee for Animal Research of Tongji Medicine College.

Additional information

Jinpeng Du and Chaojie Hu are co-first authors.

Electronic supplementary material

Table S1

(DOCX 12 kb)

Figure S1

Study flow chart. (PNG 85 kb)

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(TIF 494 kb)

Figure S2

Images of VSG before (A) and after (B) stomach resection along the greater curvature. (PNG 403 kb)

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(TIF 1187 kb)

Figure S3

Photographs of surgical implantation of an outflow catheter 1 cm below the ligament of Treitz for the collection of duodenal juice. (PNG 488 kb)

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(TIF 1319 kb)

Figure S4

Glucose transport in vitro using everted isolated jejunum loops from ND and HFD mice after a 16-week feeding. (A) Time course of mucosal-to-serosal glucose transport across the jejunum of the ND and HFD mice with or without phloretin in association with 30 mM glucose. (B) Cumulative glucose transport of jejunum segments at 60 min. Values are expressed as the means ± SEM, ***P < 0.001 vs. HFD, based on one-way analysis of variance with Bonferroni correction for multiple comparisons, n = 6 per group. (PNG 111 kb)

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(TIF 493 kb)

Figure S5

Body weight changes (A), OGTT results (B) and glucose transporter immunohistochemistry (C) of pair-fed (PF) mice, ND mice, sham mice and VSG mice at 8 weeks after surgery. Values are the means ± SEM, n = 6 per group. (PNG 1588 kb)

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(TIF 7462 kb)

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Du, J., Hu, C., Bai, J. et al. Intestinal Glucose Absorption Was Reduced by Vertical Sleeve Gastrectomy via Decreased Gastric Leptin Secretion. OBES SURG 28, 3851–3861 (2018). https://doi.org/10.1007/s11695-018-3351-4

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