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European Journal of Nutrition

, Volume 57, Issue 4, pp 1563–1575 | Cite as

Mangiferin suppresses endoplasmic reticulum stress in perivascular adipose tissue and prevents insulin resistance in the endothelium

  • Xiaoshan Xu
  • Yupeng Chen
  • Junna Song
  • Fangjie Hou
  • Xuelian Ma
  • Baolin Liu
  • Fang HuangEmail author
Original Contribution

Abstract

Purpose

Mangiferin is a naturally occurring glucosylxanthone with beneficial effects on glucose and lipid homeostasis. This study investigates the potential therapeutic effect of Mangiferin in perivascular adipose tissue (PVAT) and whether it contributes to regulating insulin action in the endothelium.

Methods

Palmitate challenge evoked ROS-associated endoplasmic reticulum stress (ER stress) and NLRP3 inflammasome activation in PVAT. The conditioned medium from PA-stimulated PVAT was prepared to induce endothelial insulin resistance, and improved endothelium-dependent vasodilation in response to insulin was detected in vitro and in vivo.

Results

Mangiferin treatment enhanced LKB1-dependent AMPK activity and suppressed ER stress with downregulation of TXNIP induction, leading to the inhibition of NLRP3 inflammasome activation evidenced by attenuated NLRP3 and cleaved caspase-1 expression as well as reduced IL-1β secretion. Moreover, Mangiferin restored insulin-mediated Akt and eNOS phosphorylations with increased NO production, immunohistochemistry examination of adipocytes, and endothelial tissue in high-fat diet-fed mice also showed that oral administration of Mangiferin inhibited ER stress and NLRP3 induction in PVAT, and then effectively prevented insulin resistance in the vessel endothelium.

Conclusions

Taken together, these results revealed that Mangiferin suppressed ER stress-associated NLRP3 inflammasome activation in PVAT through regulation of AMPK activity, which prevented endothelial insulin resistance. These findings suggested that the amelioration of PVAT dysfunction may be a therapeutic strategy for the prevention of endothelial insulin resistance.

Keywords

Mangiferin Inflammasome ER stress Insulin resistance 

Notes

Acknowledgements

This study was supported by Research project of science and technology in the Colleges and universities of Hebei Province (QN2015181) and Youth Research Fund of Hebei University of Chinese Medicine (QNZ2014016).

Compliance with ethical standards

Conflict of interest

None relevant to this study.

Supplementary material

394_2017_1441_MOESM1_ESM.tif (57 mb)
Supplementary material 1 (TIF 58395 KB)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Xiaoshan Xu
    • 1
  • Yupeng Chen
    • 1
  • Junna Song
    • 2
  • Fangjie Hou
    • 3
  • Xuelian Ma
    • 4
  • Baolin Liu
    • 1
  • Fang Huang
    • 1
    Email author
  1. 1.Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Pharmacology of Chinese Materia MedicaChina Pharmaceutical UniversityNanjingChina
  2. 2.Hebei University of Chinese Medicine, Pharmaceutical Botany OfficeHebeiChina
  3. 3.Hebei University of Chinese Medicine, Pharmacognosy OfficeHebeiChina
  4. 4.Scientific Research Center of Hebei University of Chinese MedicineHebeiChina

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