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Duodenal-Jejunal Bypass Surgery Suppresses Hepatic De Novo Lipogenesis and Alleviates Liver Fat Accumulation in a Diabetic Rat Model

Obesity Surgery volume 24, pages 2152–2160 (2014)Cite this article

Abstract

Background

Duodenal-jejunal bypass (DJB) surgery can induce rapid and durable remission of type 2 diabetes mellitus (T2DM), but the intrinsic mechanisms remain to be elucidated. Recent studies indicated that improved hepatic insulin resistance and insulin signaling transduction might contribute to the diabetic control after DJB. Given the important role of liver adiposity in hepatic insulin resistance, this study was aimed at investigating the effects of DJB on glucose homeostasis and liver fat accumulation in a T2DM rat model induced by high-fat diet (HFD) and small dose of streptozotocin (STZ).

Methods

Forty adult male diabetic rats induced by HFD and small dose of STZ were randomly assigned to sham and DJB groups. Body weight, calorie intake, hormone levels, glucose, and lipid parameters were measured at indicated time points. Subsequently, hepatic triglycerides (TG) content and the protein levels of sterol regulatory element binding protein-1 (SREBP-1), carbohydrate response element binding protein (ChREBP), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) were evaluated at 2 and 8 weeks postoperatively.

Results

Compared with sham group, DJB induced rapid and significant improvements in glucose homeostasis and insulin sensitivity independently of weight loss and calorie restriction. The DJB-operated rats exhibited lower liver TG content and decreased hepatic SREBP-1, ChREBP, ACC, and FAS at 8 weeks postoperatively.

Conclusions

DJB alleviated hepatic fat accumulation and downregulated the key transcriptional regulators and enzymes involved in hepatic de novo lipogenesis, which might contribute to improved hepatic insulin sensitivity and glucose homeostasis after DJB.

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Acknowledgment

This work was supported by the National Natural Science Foundation of China (no. 81270888/H0713, no. 81370496/H0308, no. 81300286/H0308), Shandong Provincial Outstanding Medical Academic Professional Program, Natural Science Foundation of Shandong Province Grants (no. ZR2012HQ030), and the Taishan Scholar Foundation.

Conflicts of Interest

We declare that all authors have no conflict of interest.

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Affiliations

  1. Department of General Surgery, Qilu Hospital of Shandong University, 107#, Wenhua Xi Road, Jinan, 250012, Shandong, People’s Republic of China

    Haifeng Han, Chunxiao Hu, Lei Wang, Guangyong Zhang, Shaozhuang Liu, Feng Li, Dong Sun & Sanyuan Hu

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  1. Haifeng Han
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Correspondence to Sanyuan Hu.

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Han, H., Hu, C., Wang, L. et al. Duodenal-Jejunal Bypass Surgery Suppresses Hepatic De Novo Lipogenesis and Alleviates Liver Fat Accumulation in a Diabetic Rat Model. OBES SURG 24, 2152–2160 (2014). https://doi.org/10.1007/s11695-014-1308-9

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Keywords

  • Duodenal-jejunal bypass
  • Type 2 diabetes mellitus
  • Hepatic insulin resistance
  • Liver fat content
  • De novo lipogenesis
  • High-fat diet
  • Streptozotocin