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Irisin improves fatty acid oxidation and glucose utilization in type 2 diabetes by regulating the AMPK signaling pathway

International Journal of Obesity volume 40, pages 443–451 (2016)Cite this article

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Abstract

Background/Objectives:

It has been reported that irisin regulated exercise-mediated adipocyte browning; however, the systematical effects of irisin on the metabolism of glucose and lipid in diabetes are largely unknown. In the present study, we investigated the role and underlying mechanism of irisin in glucose utilization and lipid metabolism in diabetic mice.

Methods:

A mouse model of diabetes was established by feeding C57BL/6 mice with high-fat diet. The diabetic mice were then treated with irisin. To mimic type 2 diabetes in vitro, myocytes and hepatocytes were cultured in a medium of high glucose and high fat. Glucose uptake, fatty acid oxidation and the expression of related protein were evaluated.

Results:

Irisin improved glucose tolerance and glucose uptake as evidenced by increased 18F-FDG accumulation and GLUT4 translocation in diabetic skeletal muscle. Irisin also increased glucose uptake in myocytes cultured in high glucose/high fatty acid medium. In contrast, irisin reduced the expression of PEPCK and G6Pase, which are involved in gluconeogenesis, in diabetic liver. Consistently, irisin reduced fat weight and serum total cholesterol and triglyceride levels in diabetic mice, but increased acetyl coenzyme A carboxylase-β phosphorylation in muscle tissue and uncoupling protein 1 expression in fat tissue. In addition, irisin increased the oxidation of fatty acid in myocytes. Knockdown of the adenosine monophosphate (AMP)-activated protein kinase (AMPK) attenuated the effects of irisin on glucose uptake and fatty acid β-oxidation in myocytes. Similarly, inhibition of AMPK by a specific inhibitor reduced the effects of irisin on PEPCK and G6Pase expression in hepatocytes.

Conclusions:

Our results suggest that irisin has an essential role in glucose utilization and lipid metabolism, and irisin is a promising pharmacological target for the treatment of diabetes and its complications.

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Acknowledgements

This work was supported by Program for National Science Fund for Distinguished Young Scholars of China (Grant No. 81225001), National Key Basic Research Program of China (973 Program, Grant No. 2013CB531204), New Century Excellent Talents in University (Grant No. NCET-11-0870), Program for Changjiang Scholars and Innovative Research Team in University (Grant No. PCSIRT1053), Key Science and Technology Innovation Team in Shaanxi Province (Grant No. 2014KCT-19), National Science Funds of China (Grants No. 81170186, 81470478 and 81400201).

Author contributions

The work presented here was carried out in collaboration between all authors. LT and YL defined the research theme and revised the manuscript critically. CX and JL designed methods and experiments, carried out the laboratory experiments, and wrote the paper. DZ, HW, LX, YL, JY, KL, CX, LZ and QW collected and analyzed the data, and interpreted the results.

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Author notes

  1. C Xin and J Liu: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi’an, China

    C Xin, J Liu, J Zhang, D Zhu, H Wang, Y Lee, K Lian, C Xu, L Zhang, Q Wang, Y Liu & L Tao

  2. Department of Cardiology, The Second Artillery General Hospital of Chinese Peoples’s Liberation Army, Beijing, China

    C Xin

  3. Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi’an, China

    L Xiong

  4. Department of Pathology, Xijing Hospital, The Fourth Military Medical University, Xi’an, China

    J Ye

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Xin, C., Liu, J., Zhang, J. et al. Irisin improves fatty acid oxidation and glucose utilization in type 2 diabetes by regulating the AMPK signaling pathway. Int J Obes 40, 443–451 (2016). https://doi.org/10.1038/ijo.2015.199

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