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Exploring diet-induced promoter hypomethylation and PDK4 overexpression: implications for type 2 diabetes mellitus

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Abstract

Background

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by limited metabolic flexibility in the body. Such limitation implicates the pyruvate dehydrogenase kinase 4 (PDK4) gene Poor nutrition, frequently observed among Southeast Asians usually involves excessive intakes of carbohydrates and monosodium glutamate (MSG), that have been frequently linked to an increased risk of T2DM.

Methods

The 14-week study aimed to assess the effects of high-carbohydrate (HC), high-MSG (HMSG), and a combination of high-carbohydrate and high-MSG (HCHMSG) diets on the development of T2DM using male mice. To assess the effects, the male mice were divided into four groups: control (C), HC, HMSG, and HCHMSG for 14 weeks.

Results

After 14 weeks, both the HC and HCHMSG groups showed signs of T2DM (168.83 ± 32.33; 156.42 ± 32.46). The blood samples from the HMSG, HC, and HCHMSG groups (57.67 ± 2.882; 49.22 ± 7.36; 48.9 ± 6.43) as well as skeletal muscle samples from the HMSG, HC, and HCHMSG groups (57.78 ± 8.54; 42.13 ± 7.25; 37.57 ± 10.42) exhibited a gradual hypomethylation. The HC groups particularly displayed significant PDK4 gene expression in skeletal muscle. A progressive overexpression of the PDK4 gene was observed as well in the HMSG, HCHMSG, and HC groups (2.03 ± 3.097; 3.21 ± 2.94; 5.86 ± 2.54).

Conclusions

These findings suggest that T2DM can be induced by high-carbohydrate and high-MSG diets. However, the sole consumption of high MSG did not lead to the development of T2DM. Further research should focus on conducting long-term studies to fully comprehend the impact of a high MSG diet on individuals with pre-existing T2DM.

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Data availability

Data will be made available upon request.

Abbreviations

C:

Control

FBG:

Fasting blood glucose

HC:

High-carbohydrate

HCHMSG:

High-carbohydrate and high-MSG

HMSG:

High-MSG

MSG:

Monosodium glutamate

MSP:

Methylation specific PCR

OGTT:

Oral glucose tolerance test

PDC:

Pyruvate dehydrogenase complex

PDK4:

Pyruvate dehydrogenase kinase 4

SPSS:

Statistical Package for the Social Sciences

T2DM:

Type 2 diabetes mellitus

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Acknowledgements

The researchers would like to thank the laboratory personnel at the Faculty of Biotechnology, University of Surabaya, for their invaluable support throughout the research.

Funding

The authors wish to acknowledge the financial assistance provided by the Indonesian Ministry of Research, Technology, and Higher Education for this study (058/SP-Lit/LPPM01/KemendikbudRistek/Multi/FTB/V/2022 and 004/SP2H/PT/LL7/2022).

Author information

Authors and Affiliations

  1. Faculty of Biotechnology, University of Surabaya, Surabaya, 60292, Indonesia

    Sulistyo Emantoko Dwi Putra

  2. Faculty of Medicine, University of Surabaya, Surabaya, 60292, Indonesia

    Farizky Martriano Humardani, Lisa Thalia Mulyanata, Lady Theresa Adeodata Tanaya, Heru Wijono & Risma Ikawaty

  3. Magister in Biomedical Science Program, Faculty of Medicine, Faculty of Medicine Universitas Brawijaya, Malang, 65112, Indonesia

    Farizky Martriano Humardani & Hikmawan Wahyu Sulistomo

  4. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Surabaya, Surabaya, 60292, Indonesia

    Dini Kesuma

  5. Raya Kali Rungkut Street, Surabaya, 60292, East Java, Indonesia

    Risma Ikawaty

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Contributions

SEDP, RI, and FMH performed a major part of the research work, performed statistical analysis, interpreted results, and wrote the initial draft. LTM revised the figures, improved the initial draft, and helped in lab work. LTAT also helped in lab work. HW, DK, HWS conceived the idea, supervised the work, revised, modified, and approved the final draft.

Corresponding author

Correspondence to Risma Ikawaty.

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Conflict of interest

The authors have no relevant financial or non-financial interests to disclose.

Consent for publication

This study was published with the informed consent of all authors.

Ethical approval

The study underwent a rigorous review from the Research Ethics Committee of the University of Surabaya in Indonesia to ensure that the study was conducted in a manner that respects ethical considerations and the welfare of the subjects involved. The research design received approval from the Committee on September 1, 2020 (No: 138/KE/VIII/2020). The Committee confirmed that the study met the mandatory ethical standards and abided by the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines.

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Putra, S.E.D., Humardani, F.M., Mulyanata, L.T. et al. Exploring diet-induced promoter hypomethylation and PDK4 overexpression: implications for type 2 diabetes mellitus. Mol Biol Rep 50, 8949–8958 (2023). https://doi.org/10.1007/s11033-023-08794-7

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