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Diabetes-induced cardiomyopathy is ameliorated by heat-killed Lactobacillus reuteri GMNL-263 in diabetic rats via the repression of the toll-like receptor 4 pathway

European Journal of Nutrition volume 60, pages 3211–3223 (2021)Cite this article

Abstract

Purpose

Diabetes mellitus (DM) leads to disorders such as cardiac hypertrophy, cardiac myocyte apoptosis, and cardiac fibrosis. Previous studies have shown that Lactobacillus reuteri GMNL-263 decreases cardiomyopathy by reducing inflammation. In this study, we investigated the potential benefit of GMNL-263 supplementation in treating diabetes-induced cardiomyocytes in rats with DM.

Methods

Five-week-old male Wistar rats were randomly divided into three groups, control, DM, and rats with DM treated with different dosages of L. reuteri GMNL-263. After undergoing treatment for 4 weeks, all rats were euthanized for further analysis.

Results

We observed that cardiac function and structure of rats with DM was rescued by GMNL-263. Activation of toll-like receptor 4 (TLR4)-related inflammatory, hypertrophic, and fibrotic signaling pathways in the hearts of rats with DM was reduced by treatment with GMNL-263.

Conclusion

Our findings demonstrate that GMNL-263 inhibited diabetes-induced cardiomyocytes via the repression of the TLR4 pathway. Moreover, these findings suggest that treatment with high-dose GMNL-263 could be a precautionary therapy for reducing the diabetes-induced cardiomyopathy.

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Abbreviations

CFU:

Colony-forming units

DM:

Diabetes mellitus

EF:

Ejection fraction

FS:

Percent fraction shortening

LVW:

Left ventricular weight

TGF-β:

Transforming growth factor-β

TLR4:

Toll-like receptor 4

TNF:

Tumor necrosis factor

WHW:

Whole heart weight

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Acknowledgements

We would like to thank Instrument Center of R&D Office at China Medical University for their technical assistance and Dr. Marthandam Asokan Shibu and Dr. B. Mahalakshmi, who provided suggestions during the writing of this manuscript draft. We also thank Editage for English-editing assistance.

Funding

This work was supported by grants from China Medical University, Asia University, and China Medical University Hospital (CMU101-ASIA-08, ASIA-105-CMUH-03, CMU105-S-07, and DMR107-077).

Author information

Author notes

  1. Wei-Wen Kuo and Chih-Yang Huang contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan

    Chung-Jen Chiang, Tzu-Li Lu & Sheng-Chuan Lin

  2. Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan

    Bruce Chi-Kang Tsai & Chih-Yang Huang

  3. Department of Chemical Engineering, Feng Chia University, Taichung, Taiwan

    Yun-Peng Chao & Pin-Ning Wang

  4. Department of Nursing, MeiHo University, Pingtung, Taiwan

    Cecilia Hsuan Day

  5. Department of Chinese Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan

    Tsung-Jung Ho

  6. Integration Center of Traditional Chinese and Modern Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan

    Tsung-Jung Ho

  7. School of Post-Baccalaureate Chinese Medicine, College of Medicine, Tzu Chi University, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan

    Tsung-Jung Ho

  8. Department of Biotechnology, Bharathiar University, Coimbatore, India

    V. Vijaya Padma

  9. Department of Biological Science and Technology, China Medical University, Taichung, Taiwan

    Wei-Wen Kuo

  10. Ph.D. Program for Biotechnology Industry, China Medical University, Taichung, Taiwan

    Wei-Wen Kuo

  11. Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

    Chih-Yang Huang

  12. Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan

    Chih-Yang Huang

  13. Department of Biological Science and Technology, Asia University, Taichung, Taiwan

    Chih-Yang Huang

  14. Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien, Taiwan

    Chih-Yang Huang

Authors
  1. Chung-Jen Chiang
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  2. Bruce Chi-Kang Tsai
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  5. Cecilia Hsuan Day
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  9. V. Vijaya Padma
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  10. Wei-Wen Kuo
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  11. Chih-Yang Huang
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Contributions

CJC, TLL, YPC, and CYH conceptualized and designed the study. PNW, SCL, and BCKT collected and assembled the data. CHD, CJC, and YPC provided materials for the study. PNW, SCL, and BCKT analyzed and interpreted the data. SCL and BCKT wrote the draft of the manuscript. TJH, WWK and CYH reviewed and gave the final approval of the manuscript. TJH, VVP, and WWK provided the administrative support, and WWK and CYH provided financial support.

Corresponding author

Correspondence to Chih-Yang Huang.

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No conflicts of interest, financial or otherwise, are declared by the authors.

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Chiang, CJ., Tsai, B.CK., Lu, TL. et al. Diabetes-induced cardiomyopathy is ameliorated by heat-killed Lactobacillus reuteri GMNL-263 in diabetic rats via the repression of the toll-like receptor 4 pathway. Eur J Nutr 60, 3211–3223 (2021). https://doi.org/10.1007/s00394-020-02474-z

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Keywords

  • Diabetes mellitus
  • Cardiomyopathy
  • GMNL-263
  • TLR4
  • TGF-β