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Adrenomedullin ameliorates palmitic acid-induced insulin resistance through PI3K/Akt pathway in adipocytes

Abstract

Aims

White adipose tissue (WAT) dysfunction has been associated with adipose tissue low-grade inflammation and oxidative stress leading to insulin resistance (IR). Adrenomedullin (ADM), an endogenous active peptide considered as an adipokine, is associated with adipocytes function.

Methods

We evaluated the protective effects of ADM against IR in 3T3-L1 adipocytes treated by palmitic acid (PA) and in visceral white adipose tissue (vWAT) of obese rats fed with high-fat diet.

Results

We found that endogenous protein expressions of ADM and its receptor in PA-treated adipocytes were markedly increased. PA significantly induced impaired insulin signaling by affecting phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) axis and glucose transporter-4 (GLUT-4) levels, whereas ADM pretreatment enhanced insulin signaling PI3K/Akt and GLUT-4 membrane protein levels, decreased pro-inflammatory cytokines tumor necrosis factor α (TNFα), interleukin-1β (IL-1β) and IL-6 levels, and improved oxidative stress accompanied with reduced reactive oxygen species (ROS) levels and increased anti-oxidant enzymes manganese superoxide dismutase 2 (SOD2), glutathione peroxidase (GPx1) and catalase (CAT) protein expressions. Furthermore, ADM treatment not only improved IR in obese rats, but also effectively restored insulin signaling, and reduced inflammation and oxidative stress in vWAT of obese rats.

Conclusions

This study demonstrates a prevention potential of ADM against obesity-related metabolic disorders, due to its protective effects against IR, inflammation and oxidative stress in adipocytes.

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Availability of data and materials

The datasets used and/or analyzed in this study will be made available by the authors on reasonable request.

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Acknowledgements

We gratefully acknowledge support by the National Natural Science Foundation of China (81970356 and 81470539) and the generous support of the Collaborative Innovation Center for Cardiovascular Disease Translational Medicine.

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Authors

Contributions

All authors reviewed of the manuscript. Ye-Bo Zhou designed the study. Hang-Bing Dai, Hong-Yu Wang, Pei-Qian and Hong Zhou conducted the experiments. Fang-Zheng Wang and Qing Gao performed the data analysis. Hang-Bing Dai and Ye-Bo Zhou wrote the manuscript. Ye-Bo Zhou revised the manuscript.

Corresponding author

Correspondence to Ye-Bo Zhou.

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Dai, HB., Wang, HY., Wang, FZ. et al. Adrenomedullin ameliorates palmitic acid-induced insulin resistance through PI3K/Akt pathway in adipocytes. Acta Diabetol 59, 661–673 (2022). https://doi.org/10.1007/s00592-021-01840-5

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  • DOI: https://doi.org/10.1007/s00592-021-01840-5

Keywords

  • Adrenomedullin
  • Insulin resistance
  • Inflammation
  • Oxidative stress
  • PI3K/Akt pathway