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

Journal of Diabetes & Metabolic Disorders - Tập 22 - Trang 487-494 - 2022
Nobunao Ikewaki1,2, Yasunori Ikeue3, Mitsuru Nagataki3, Gene Kurosawa4,5, Vidyasagar Devaprasad Dedeepiya6, Mathaiyan Rajmohan7, Suryaprakash Vaddi8, Rajappa Senthilkumar7, Senthilkumar Preethy7, Samuel J. K. Abraham3,6,9,10
1Department of Medical Life Science, Kyushu University of Health and Welfare, Nobeoka, Japan
2Institute of Immunology, Junsei Educational Institute, Nobeoka, Japan
3Sophy Inc., Kochi, Japan
4Department of Academic Research Support Promotion Facility, Center for Research Promotion and Support, Fujita Health University, Aichi, Japan
5MabGenesis KK, Nagoya, Japan
6Mary-Yoshio Translational Hexagon (MYTH), Nichi-In Centre for Regenerative Medicine (NCRM), Chennai, India
7Fujio-Eiji Academic Terrain (FEAT), Nichi-In Centre for Regenerative Medicine (NCRM), Chennai, India
8Department of Urology, Yashoda Hospitals, Hyderabad, India
9Centre for Advancing Clinical Research (CACR), University of Yamanashi - School of Medicine, Chuo, Japan
10Antony- Xavier Interdisciplinary Scholastics (AXIS), GN Corporation Co. Ltd., Kofu, Japan

Tóm tắt

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. 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. 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. 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).

Tài liệu tham khảo

The Nomenclature of Lipids. https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1977.tb11778.x. Accessed 10 Dec 2022. Boden G. Obesity, insulin resistance and free fatty acids. Curr Opin Endocrinol Diabetes Obes. 2011;18(2):139–43. Holt HB, Wild SH, Wood PJ, Zhang J, Darekar AA, Dewbury K, Poole RB, Holt RI, Phillips DI, Byrne CD. Non-esterified fatty acid concentrations are independently associated with hepatic steatosis in obese subjects. Diabetologia. 2006;49(1):141–8. Yazıcı D, Sezer H. Insulin resistance, obesity and lipotoxicity. Adv Exp Med Biol. 2017;960:277–304. Fazio S. Fibrates — The Other Life-saving Lipid Drugs US Cardiology 2004;1(1):1–6. Cloetens L, Ulmius M, Johansson-Persson A, Akesson B, Onning G. Role of dietary beta-glucans in the prevention of the metabolic syndrome. Nutr Rev. 2012;70(8):444–58. Akramiene D, Kondrotas A, Didziapetriene J, Kevelaitis E. Effects of beta-glucans on the immune system. Medicina (Kaunas). 2007;43(8):597–606 (6777). Dedeepiya V, Sivaraman G, Venkatesh A, Preethy S, Abraham S. Potential effects of Nichi glucan as a food supplement for diabetes mellitus and hyperlipidemia; preliminary findings from the study on three patients from India. Case Rep Med. 2012;2012:895370. https://doi.org/10.1155/2012/895370. https://www.biorxiv.org/content/10.1101/2021.07.22.453362v3. Accessed 10 Dec 2022. Ganesh JS, Rao YY, Ravikumar R, Jayakrishnan AG, Iwasaki M, Preethy S, Abraham S. Beneficial effects of Black yeast derived 1–3, 1–6 beta glucan- Nichi Glucan in a dyslipidemic individual of Indian origin - A case report. J Diet Suppl. 2014;11(1):1–6. Ikewaki N, Sonoda T, Kurosawa G, Iwasaki M, Dedeepiya VD, Senthilkumar R, Preethy S, Abraham SJK. Immune and metabolic beneficial effects of Beta 1,3–1,6 glucans produced by two novel strains of Aureobasidium pullulans in healthy middle-aged Japanese men: An exploratory study. medRxiv 2021.08.05.21261640; https://doi.org/10.1101/2021.08.05.21261640. Castle CK, Colca JR, Melchior GW. Lipoprotein profile characterization of the KKA(y) mouse, a rodent model of type II diabetes, before and after treatment with the insulin-sensitizing agent pioglitazone. Arterioscler Thromb. 1993;13(2):302–9. Lian Y, Xie L, Liu Y, Tang F. Metabolic-related markers and inflammatory factors as predictors of dyslipidemia among urban Han Chinese adults. Lipids Health Dis. 2019;18(1):167. Liu J, Han L, Zhu L, Yu Y. Free fatty acids, not triglycerides, are associated with non-alcoholic liver injury progression in high fat diet induced obese rats. Lipids Health Dis. 2016;11(15):27. Boden G. Free fatty acids, insulin resistance, and type 2 diabetes mellitus. Proc Assoc Am Phys. 1999;111(3):241–8. Zhang J, Zhao Y, Xu C, Hong Y, Lu H, Wu J, Chen Y. Association between serum free fatty acid levels and nonalcoholic fatty liver disease: a cross-sectional study. Sci Rep. 2014;25(4):5832. Bunn RC, Cockrell GE, Ou Y, Thrailkill KM, Lumpkin CK Jr, Fowlkes JL. Palmitate and insulin synergistically induce IL-6 expression in human monocytes. Cardiovasc Diabetol. 2010;5(9):73. Zhu Y, Yao Y, Gao Y, Hu Y, Shi Z, Ren G. Suppressive effects of barley β-Glucans with different molecular weight on 3T3-L1 Adipocyte differentiation. J Food Sci. 2016;81(3):H786–93. Rodrigues MV, Zanuzzo FS, Koch JFA, de Oliveira CAF, Sima P, Vetvicka V. Development of fish immunity and the role of β-Glucan in immune responses. Molecules. 2020;25:5378. Ikewaki N, Fujii N, Onaka T, Ikewaki S, Inoko H. Immunological actions of Sophy beta-glucan (beta-1,3–1,6 glucan), currently available commercially as a health food supplement. Microbiol Immunol. 2007;51(9):861–73. Ikewaki M, Iwasaki M, Kurosawa G, Rao KS, Beitia JL, Preethy S, Abraham SJ. β-Glucans: Wide-spectrum Immune-balancing Food-supplement-based Enteric (β-WIFE) Vaccine Adjuvant Approach to COVID-19. Hum Vaccin Immunother 2021; 17. https://doi.org/10.1080/21645515.2021.1880210. Noss I, Ozment TR, Graves BM, Kruppa MD, Rice PJ, Williams DL. Cellular and molecular mechanisms of fungal β-(1→6)-glucan in macrophages. Innate Immun. 2015;21:759–69. Samkani A, Skytte MJ, Anholm C, Astrup A, Deacon CF, Holst JJ, Madsbad S, Boston R, Krarup T, Haugaard SB. The acute effects of dietary carbohydrate reduction on postprandial responses of non-esterified fatty acids and triglycerides: a randomized trial. Lipids Health Dis. 2018;17(1):295. Ikewaki N, Kurosawa G, Iwasaki M, Preethy S, Dedeepiya VD, Vaddi S, Senthilkumar R, Levy GA, Abraham SJK. Hepatoprotective effects of Aureobasidium pullulans derived Beta 1,3–1,6 biological response modifier glucans in a STAM- animal model of non-alcoholic steatohepatitis. J Clin Exp Hepatol. 2022. https://doi.org/10.1016/j.jceh.2022.06.008.