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Gastric Sleeve Surgery Alleviates Obesity-Associated Insulin Resistance and Suppresses Endoplasmic Reticulum Stress in Adipose Tissue of db/db Mice

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Abstract

Objective

The aims of this study were to evaluate the effects of gastric sleeve surgery on diabetes remission in db/db mice as well as to determine the underlying mechanisms.

Methods

Thirty spontaneously obese, diabetic mice (C57BL/Ksj-db/db) were randomly divided into three groups: sleeve gastrectomy group, sham-operated group, and control db/db group. Ten db/m lean mice were used as nondiabetic littermate controls. All mice were sacrificed on day 28. The fasting plasma glucose, serum insulin, lipid profile, and oral glucose tolerance were measured pre- and postoperatively. Inflammatory cytokines (TNF-α and IL-6), endoplasmic reticulum (ER) stress–related markers (GRP78, PERK, IRE-1, and ATF6), and glucose transporter 4 (GLUT4) in the adipose tissue were assayed.

Results

Sleeve gastrectomy significantly reduced the body weight and food intake in the db/db mice. This surgery improved glucose and lipid metabolism, as manifested by the decrease in the fasting plasma glucose level and partial restoration of lipid abnormalities. Also, the surgery improved glucose tolerance and alleviated insulin resistance in db/db mice. Sleeve gastrectomy surgery induced downregulation of the inflammatory adipocytokines TNF-α and IL-6; suppressed expression of the ER stress–related markers GRP78, PERK, IRE-1, and ATF-6; and increased the expression and distribution of GLUT4 in adipose tissue of db/db mice.

Conclusion

The improvement in glucose tolerance following sleeve gastrectomy is associated with alleviation of insulin resistance, reduction of inflammatory adipocytokine levels, and suppression of ER stress. Further studies are needed to assess whether these effects have a causal role.

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Funding

This work was supported by the Shenyang Science and Technology Project (No. 150422): The effects of gastric sleeve surgery on caveolin-1 expression and its role in alleviating the insulin resistance and the endoplasmic reticulum stress in adipose tissue; and the Liaoning Natural Science Foundation (No. 2015020505): Mechanism of bariatric surgery affecting the insulin resistance and endoplasmic reticulum stress in adipose tissue.

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Author notes

  1. Ming Sun and Wenyan Zhao contributed equally to this work.

Authors and Affiliations

  1. Department of Urology, Shengjing Hospital of China Medical University, Shenyang, 110004, Liaoning Province, People’s Republic of China

    Ming Sun

  2. Department of General Surgery, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning Province, People’s Republic of China

    Wenyan Zhao, Shuqiang Li, Chunfei Li, Yong Feng & Donghua Geng

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  1. Ming Sun
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  2. Wenyan Zhao
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  4. Chunfei Li
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  5. Yong Feng
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  6. Donghua Geng
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Corresponding author

Correspondence to Donghua Geng.

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Conflict of Interest

The authors declare that they have no conflicts of interest.

Ethical Approval

The experimental protocols were approved by the Ethics Committee of Shengjing Hospital of China Medical University. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Supplementary Figure 1

Expression of IL-6 and TNF-α in epididymal adipose tissue. (A) IL-6 mRNA level; (B) IL-6 protein level; (C) TNF-α mRNA level; (D) TNF-α protein level. *P < 0.01 compared with the db/db-control or db/db-sham group; #P < 0.01 compared with all the db/m subgroups. IL-6, interleukin 6; TNF-α, tumor necrosis factor-α. (PNG 551 kb)

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Sun, M., Zhao, W., Li, S. et al. Gastric Sleeve Surgery Alleviates Obesity-Associated Insulin Resistance and Suppresses Endoplasmic Reticulum Stress in Adipose Tissue of db/db Mice. OBES SURG 29, 3220–3227 (2019). https://doi.org/10.1007/s11695-019-03966-6

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  • DOI: https://doi.org/10.1007/s11695-019-03966-6

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