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Beneficial effects of 1,3–1,6 β-glucans produced by Aureobasidium pullulans on non-esterified fatty acid levels in diabetic KKAy mice and their potential implications in metabolic dysregulation

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Abstract

Objectives

In this study, we used an obese and diabetic mouse model to compare two strains of Aureobasidium pullulans (AFO-202 and N-163) produced beta-glucans (β-glucans), which alleviate lipotoxicity.

Methods

Four groups of KK-Ay mice were used, with six subjects in each group. Group 1: sacrificed on day 0 for baseline values; Group 2: control (drinking water); Group 3: AFO-202 beta glucan—200 mg/kg/day; Group 4: N-163 beta glucan—300 mg/kg/day for 28 consecutive days.

Results

Group 4 (N-163) had the lowest non-esterified fatty acids (NEFA) levels and marginally decreased triglyceride levels compared to the other groups. There were no significant differences in blood glucose, hemoglobin A1c (HbA1c), triglycerides, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol levels. N-163 β-glucans decreased NEFA levels after 28 days.

Conclusion

These results, although modest, warrant further in-depth research into lipotoxicity and associated inflammatory cascades in both healthy and diseased subjects for the prevention and management of metabolic dysregulation and associated diseases such as non-alcoholic fatty liver disease (NAFLD).

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Data availability

All data generated or analysed during this study are included in this manuscript.

Abbreviations

NEFA:

Non-esterified fatty acids

FFA:

Free fatty acids

NASH:

Non-alcoholic steatohepatitis

PDA:

Potato dextrose agar

PDB:

Potato dextrose broth

LDL:

Low-density lipoprotein

HDL:

High-density lipoprotein

ANOVA:

Analysis of variance

NAFLD:

Non-alcoholic fatty liver disease

STAM:

Stelic animal model

TNF:

Tumour necrosis factor

IL:

Interleukin

PPARγ:

Peroxisome proliferator-activated receptor γ

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Acknowledgements

The authors would like to dedicate this paper to the memory of Mr. Takashi Onaka, who passed away on the 1st of June, 2022 at the age of 90 years, who played a pivotal role in successfully culturing and industrial scale up of AFO-202 and N-163 strains of Aureobasidium pullulans after their isolation and standardization of the process of producing the novel beta glucans described in this study.

The authors thank

a. Mr. Yoshio Morozumi, Ms. Yoshiko Amikura of GN Corporation, Japan for their liaison assistance with the conduct of the study.

b. Ms. Eiko Amemiya of the II Department of Surgery, University of Yamanashi for her secretarial assistance.

c. Loyola-ICAM College of Engineering and Technology (LICET) for their support to our research work.

Author information

Authors and Affiliations

  1. Department of Medical Life Science, Kyushu University of Health and Welfare, Nobeoka, Japan

    Nobunao Ikewaki

  2. Institute of Immunology, Junsei Educational Institute, Nobeoka, Miyazaki, Japan

    Nobunao Ikewaki

  3. Sophy Inc., Kochi, Japan

    Yasunori Ikeue, Mitsuru Nagataki & Samuel J. K. Abraham

  4. Department of Academic Research Support Promotion Facility, Center for Research Promotion and Support, Fujita Health University, Aichi, Japan

    Gene Kurosawa

  5. MabGenesis KK, Nagoya, Japan

    Gene Kurosawa

  6. Mary-Yoshio Translational Hexagon (MYTH), Nichi-In Centre for Regenerative Medicine (NCRM), Chennai, India

    Vidyasagar Devaprasad Dedeepiya & Samuel J. K. Abraham

  7. Fujio-Eiji Academic Terrain (FEAT), Nichi-In Centre for Regenerative Medicine (NCRM), Chennai, India

    Mathaiyan Rajmohan, Rajappa Senthilkumar & Senthilkumar Preethy

  8. Department of Urology, Yashoda Hospitals, Hyderabad, India

    Suryaprakash Vaddi

  9. Centre for Advancing Clinical Research (CACR), University of Yamanashi - School of Medicine, Chuo, Japan

    Samuel J. K. Abraham

  10. Antony- Xavier Interdisciplinary Scholastics (AXIS), GN Corporation Co. Ltd., 3-8, Wakamatsu, Kofu, Yamanashi, 400-0866, Japan

    Samuel J. K. Abraham

Authors
  1. Nobunao Ikewaki
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  2. Yasunori Ikeue
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  8. Rajappa Senthilkumar
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Contributions

N.I and S.A. contributed to conception and design of the study. Y.I and M.N helped with technical assistance. R.S helped in literature search. S.A, M.R and S.P. drafted the manuscript. G.K, V.D and S.V performed critical revision of the manuscript. All the authors read, and approved the submitted version.

Corresponding author

Correspondence to Samuel J. K. Abraham.

Ethics declarations

Ethics approval

The protocol approval was obtained from the ethics committee of Toya Laboratory, HOKUDO Co., Japan (Ref no: HKD47047). The study was conducted in accordance with the HOKUDO Animal Experiment Regulations following the Act on Welfare and Management of Animals (Ministry of the Environment, Japan, Act No. 105 of October 1, 1973), standards relating to the care and management of laboratory animals and relief of pain (Notice No.88 of the Ministry of the Environment, Japan, April 28, 2006) and the guidelines for proper conduct of animal experiments (Science Council of Japan, June 1, 2006). All animal experiments took place at Toya Laboratory, HOKUDO Co., Hokkaido, Japan.

Potential conflict of interests

Author Samuel Abraham is a shareholder in GN Corporation, Japan which holds shares of Sophy Inc., Japan., the manufacturers of novel beta glucans using different strains of Aureobasidium pullulans; a board member in both the companies and also an applicant to several patents of relevance to these beta glucans.

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The article has been posted on the preprint server, bioRxiv, https://doi.org/10.1101/2021.07.22.453362

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Ikewaki, N., Ikeue, Y., Nagataki, M. et al. Beneficial effects of 1,3–1,6 β-glucans produced by Aureobasidium pullulans on non-esterified fatty acid levels in diabetic KKAy mice and their potential implications in metabolic dysregulation. J Diabetes Metab Disord 22, 487–494 (2023). https://doi.org/10.1007/s40200-022-01170-5

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