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Roux-en-Y Gastric Bypass Surgery Suppresses Hepatic Gluconeogenesis and Increases Intestinal Gluconeogenesis in a T2DM Rat Model

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Abstract

Background

Roux-en-Y gastric bypass (RYGB) is an effective surgical treatment for type 2 diabetes mellitus (T2DM). The present study aimed to investigate the effects of RYGB on glucose homeostasis, lipid metabolism, and intestinal morphological adaption, as well as hepatic and intestinal gluconeogenesis.

Methods

Twenty adult male T2DM rats induced by high-fat diet and low dose of streptozotocin were randomly divided into sham and RYGB groups. The parameters of body weight, food intake, glucose tolerance, insulin sensitivity, and serum lipid profiles were assessed to evaluate metabolic changes. Intestinal sections were stained with hematoxylin and eosin (H&E) for light microscopy examination. The messenger RNA (mRNA) and protein expression levels of key regulatory enzymes of gluconeogenesis [phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase)] were determined through reverse-transcription PCR (RT-PCR) and Western blotting, respectively.

Results

RYGB induced significant improvements in glucose tolerance and insulin sensitivity, along with weight loss and decreased food intake. RYGB also decreased serum triglyceride (TG) and free fatty acid (FFA) levels. The jejunum and ileum exhibited a marked increase in the length and number of intestinal villi after RYGB. The RYGB group exhibited downregulated mRNA and protein expression levels of PEPCK and G6Pase in the liver and upregulated expression of these enzymes in the jejunum and ileum tissues.

Conclusions

RYGB ameliorates glucose and lipid metabolism accompanied by weight loss and calorie restriction. The small intestine shows hyperplasia and hypertrophy after RYGB. Meanwhile, our study demonstrated that the reduced hepatic gluconeogenesis and increased intestinal gluconeogenesis may contribute to improved glucose homeostasis after RYGB.

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Acknowledgments

This work was supported by the Key Project of Shanghai Health and Family Planning Commission (Grant No. 201440026).

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Author notes

    Authors and Affiliations

    1. Department of General Surgery, Central Hospital of Fengxian District, Southern Medical University, No.6600, Nan Feng Road, Shanghai, 201499, China

      Yong Yan, Fanzhi Kong, Suibin Feng, Xuzhong Li, Guangjun Zhang, Haijun Liu, Haiqing Zhang, Shiguang Wang & Xueli Zhang

    2. Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 200233, China

      Zhou Zhou & Cheng Hu

    3. Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China

      Yanhua Sha

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    1. Yong Yan
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    Correspondence to Cheng Hu or Xueli Zhang.

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    Informed consent does not apply to this study.

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    All applicable institutional and national guidelines for the care and use of animals were followed.

    Additional information

    Yong Yan and Zhou Zhou contributed equally to this work. Cheng Hu and Xueli Zhang contributed equally to this work.

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    Yan, Y., Zhou, Z., Kong, F. et al. Roux-en-Y Gastric Bypass Surgery Suppresses Hepatic Gluconeogenesis and Increases Intestinal Gluconeogenesis in a T2DM Rat Model. OBES SURG 26, 2683–2690 (2016). https://doi.org/10.1007/s11695-016-2157-5

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