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Adiponectin/SIRT1 Axis Induces White Adipose Browning After Vertical Sleeve Gastrectomy of Obese Rats with Type 2 Diabetes

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Abstract

Purpose

White adipose tissue (WAT) browning plays a crucial role in energy metabolism. However, it remains unclear whether WAT browning is involved in the adipose reduction following sleeve gastrectomy (SG). Adiponectin is upregulated after Roux-en-Y gastric bypass surgery. The role of adiponectin in SG was further investigated in the current study.

Materials and Methods

Diabetic Sprague Dawley rats were randomly divided into control, sham + libitum, sham + food restriction, and sleeve groups. Browning markers, including uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor (PPAR) γ, and PPARγ coactivator-1 alpha (PGC-1α), were examined 4 weeks after the operation.

Results

UCP1, PPARγ, and PGC-1α expression were significantly higher in the sleeve group compared to the other study groups. The adipose tissue of the sleeve group exhibited tissue weight loss and additional morphological browning features. In addition, adiponectin expression in the sleeve group was significantly increased. Adiponectin upregulated the expression of the browning genes and sirtuin 1 (SIRT1) in 3T3-L1 adipocytes. SIRT1 could increase the WAT browning levels, revealing that adiponectin induced the browning process via the upregulation of SIRT1. Furthermore, SIRT1 represented a positive regulatory feedback loop for adiponectin. SIRT1 activated adenosine monophosphate-activated protein kinase (AMPK), which can mediate WAT browning. Inhibition of the AMPK signaling pathway by dorsomorphin decreased UCP1, PPARγ, and PGC-1α expression. However, additional studies are needed to understand the relationship between adiponectin and glucose homeostasis.

Conclusions

Sleeve gastrectomy increased adiponectin levels, which in turn upregulated SIRT1. Thus, SIRT1 may function as an endocrine signal to mediate WAT browning.

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Funding

This study was funded by the National Natural Science Foundation of China (No. 81702402, No. 81570765, No. 81802760) and Science and Technology Project of Liaoning (No. 20170520027, No. 201602866, No. 2015020539).

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Authors and Affiliations

  1. Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, 110004, People’s Republic of China

    Lei Liu

  2. Department of General Surgery, The Forth Hospital of China Medical University, Shenyang, 110032, People’s Republic of China

    Lei Liu, Tianyi Zhang, Jingyao Hu, Mofei Wang & Yong Wang

  3. Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, 110004, People’s Republic of China

    Rui Ma & Bing He

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  1. Lei Liu
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  2. Tianyi Zhang
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  5. Bing He
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  7. Yong Wang
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Contributions

Lei Liu:Models construction and samples obtaining and manuscript writing

Tianyi Zhang:Cell culture and transfection

Jingyao Hu:Western blot

Rui Ma:PCR

Bing He:Immunohistocheistry staining

Mofei Wang:Data Statistics

Yong Wang:Responsible for study design

Corresponding author

Correspondence to Yong Wang.

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Ethical Approval and Animal Welfare

The study was approved by an animal care committee of Shengjing Hospital. The welfare of animals used for research was respected. All applicable institutional and/or national guidelines for the care and use of animals were followed. This article does not contain any studies with human participants, and informed consent is not required.

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The authors declare that they have no conflict of interest.

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Liu, L., Zhang, T., Hu, J. et al. Adiponectin/SIRT1 Axis Induces White Adipose Browning After Vertical Sleeve Gastrectomy of Obese Rats with Type 2 Diabetes. OBES SURG 30, 1392–1403 (2020). https://doi.org/10.1007/s11695-019-04295-4

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