The Effects of Soyferment-Tempeh on Lipid Profile, Retinol-Binding Protein 4 (RBP4), and Phosphoenolpyruvate Carboxykinase (PEPCK) Gene Expression in Type 2 Diabetic Mice

  • Prasetyastuti Prasetyastuti Faculty of Medicine, Public Health and Nursing Universitas Gadjah Mada, Yogyakarta, Jl. Kaliurang Km.4 Sekip Utara 55281, Indonesia
  • Dian Setiawan Ghozali Post-graduate student of Biomedical Science; major in Biochemistry, Faculty of Medicine, Public Health and Nursing Universitas Gadjah Mada, Yogyakarta
Keywords: Soyferment-Tempeh, Lipid Profile, Atherogenic Index, Retinol-Binding Protein 4, Phosphoenol Pyruvate Carboxykinase

Abstract

Diabetes Type 2 can cause oxidative stress leading to the accumulation of reactive oxygen species. Soyferment-Tempeh, a fermented soybean product with aerobic and anaerobic R. oligosporus incubation has a high antioxidant content of isoflavones that can regulate oxidative stress in diabetes. In this study, we evaluate the effects of Soyferment-Tempeh on lipid profile, Retinol-Binding Protein 4 (RBP4), and Phosphoenolpyruvate Carboxykinase (PEPCK) gene expression in type 2 diabetic mice. A total of 30 mice with the age of eight weeks were divided into six groups as follows: A) nondiabetic, B) diabetic mice, C) diabetic mice with metformin, D), E), and F) diabetic mice with Soyferment-Tempeh doses of 10, 20, or 40mg/100g body weight (BW), respectively, were administered treatments orally by gavages. Blood was collected for assessment of blood glucose level, and lipid profile before and after 3 weeks of the administration. After sacrificing the mice, livers were used for RBP4 and PEPCK gene expression assessment. Supplementation with three different doses of Soyferment-Tempeh in streptozotocin-induced diabetic mice for 21 days significantly (p<0.001) reduced blood glucose level, total cholesterol, triglycerides, low-density lipoprotein level, atherogenic index, and increased high-density lipoprotein level. There was a significant decrease in RBP4 gene expression in the Soyferment-Tempeh of dose 10mg/100g BW treatment groups (p<0.05), while the PEPCK gene expression did not significantly differ (p>0.05). These results demonstrate that supplementation with Soyferment-Tempeh decreases blood glucose level, atherogenic index, improves lipid profile, and decreases RBP4.

References

Aoki, H., Uda, I., Tagami, K., Furuya, Y., Endo, Y., & Fujimoto, K. (2003). The production of a new tempeh-like fermented soybean containing a high level of gamma-aminobutyric acid by anaerobic incubation with Rhizopus. Bioscience, biotechnology, and biochemistry, 67(5), 1018–1023. https://doi.org/10.1271/bbb.67.1018
Berry, D., Noy, N. (2017). Retinol Binding Protein 4: Role in Diabetes and Cancer. Adipocytokines, Energy Balance, and Cancer. Energy Balance and Cancer. 12. Switzerland: Springer International Publishing Services. p. 89-107.
Duru, K. C., Kovaleva, E. G., Danilova, I. G., van der Bijl, P., & Belousova, A. V. (2018). The potential beneficial role of isoflavones in type 2 diabetes mellitus. Nutrition research (New York, N.Y.), 59, 1–15. https://doi.org/10.1016/j.nutres.2018.06.005.
El-Kordy, E. A., & Alshahrani, A. M. (2015). Effect of genistein, a natural soy isoflavone, on pancreatic β-cells of streptozotocin-induced diabetic rats: Histological and immunohistochemical study. Journal of microscopy and ultrastructure,3(3),108–119. https://doi.org/10.1016/j.jmau.2015.03.005.
Graham, T. E., Yang, Q., Blüher, M., Hammarstedt, A., Ciaraldi, T. P., Henry, R. R., Wason, C. J., Oberbach, A., Jansson, P. A., Smith, U., & Kahn, B. B. (2006). Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects. The New England journal of medicine, 354(24), 2552–2563. https://doi.org/10.1056/NEJMoa054862.
Haron, H., Ismail, A., Azlan, A., Shahar, S., Su Peng, L. (2009). Daidzein and genestein contents in tempeh and selected soy products. Food Chemistry.115(4),1350-1356. https://doi.org/10.1016/j.foodchem.2009.01.053
Hatting, M., Tavares, C., Sharabi, K., Rines, A. K., & Puigserver, P. (2018). Insulin regulation of gluconeogenesis. Annals of the New York Academy of Sciences, 1411(1), 21–35. https://doi.org/10.1111/nyas.13435.
Huang, Y. C., Wu, B. H., Chu, Y. L., Chang, W. C., & Wu, M. C. (2018). Effects of Tempeh Fermentation with Lactobacillus plantarum and Rhizopus oligosporus on Streptozotocin-Induced Type II Diabetes Mellitus in Rats. Nutrients, 10(9), 1143. https://doi.org/10.3390/nu10091143
Lee, J., Yee, S. T., Kim, J. J., Choi, M. S., Kwon, E. Y., Seo, K. I., & Lee, M. K. (2010). Ursolic acid ameliorates thymic atrophy and hyperglycemia in streptozotocin-nicotinamide-induced diabetic mice. Chemico-biological interactions, 188(3), 635–642. https://doi.org/10.1016/j.cbi.2010.09.019
Lee J. S. (2006). Effects of soy protein and genistein on blood glucose, antioxidant enzyme activities, and lipid profile in streptozotocin-induced diabetic rats. Life sciences, 79(16), 1578–1584. https://doi.org/10.1016/j.lfs.2006.06.030
Liu, Y., Wang, D., Li, D., Sun, R., & Xia, M. (2014). Associations of retinol-binding protein 4 with oxidative stress, inflammatory markers, and metabolic syndrome in a middle-aged and elderly Chinese population. Diabetology & metabolic syndrome, 6(1), 25. https://doi.org/10.1186/1758-5996-6-25
Rocha, M., Bañuls, C., Bellod, L., Rovira-Llopis, S., Morillas, C., Solá, E., Víctor, V. M., & Hernández-Mijares, A. (2013). Association of serum retinol binding protein 4 with atherogenic dyslipidemia in morbid obese patients. PloS one, 8(11), e78670. https://doi.org/10.1371/journal.pone.0078670
Shim, J. Y., Kim, K. O., Seo, B. H., & Lee, H. S. (2007). Soybean isoflavone extract improves glucose tolerance and raises the survival rate in streptozotocin-induced diabetic rats. Nutrition research and practice, 1(4), 266–272. https://doi.org/10.4162/nrp.2007.1.4.266
Sun, L., Qi, Q., Zong, G., Ye, X., Li, H., Liu, X., Zheng, H., Hu, F. B., Liu, Y., & Lin, X. (2014). Elevated plasma retinol-binding protein 4 is associated with increased risk of type 2 diabetes in middle-aged and elderly Chinese adults. The Journal of nutrition, 144(5), 722–728. https://doi.org/10.3945/jn.113.189860
Tamori, Y., Sakaue, H., & Kasuga, M. (2006). RBP4, an unexpected adipokine. Nature medicine, 12(1),30–31. https://doi.org/10.1038/nm0106-30
Tsutsumi, C., Okuno, M., Tannous, L., Piantedosi, R., Allan, M., Goodman, D. S., & Blaner, W. S. (1992). Retinoids and retinoid-binding protein expression in rat adipocytes. The Journal of biological chemistry, 267(3), 1805–1810.
Valverde AM, Burks DJ, Fabregat I, Fisher TL, Carretero J, White MF, Benito M. Molecular mechanisms of insulin resistance in IRS-2-deficient hepatocytes. Diabetes. 2003 Sep;52(9):2239-48. doi: 10.2337/diabetes.52.9.2239. PMID: 12941762.
van der Velpen, V., Geelen, A., Hollman, P. C., Schouten, E. G., van 't Veer, P., & Afman, L. A. (2014). Isoflavone supplement composition and equol producer status affect gene expression in adipose tissue: a double-blind, randomized, placebo-controlled crossover trial in postmenopausal women. The American journal of clinical nutrition, 100(5), 1269–1277. https://doi.org/10.3945/ajcn.114.088484
Vergès, B., Guiu, B., Cercueil, J. P., Duvillard, L., Robin, I., Buffier, P., Bouillet, B., Aho, S., Brindisi, M. C,, Petit, J. M. (2012). Retinol-binding protein 4 is an independent factor associated with triglycerides and a determinant of very low-density lipoprotein-apolipoprotein b100 catabolism in type 2 diabetes mellitus. Arteriosclerosis, Thrombosis, and Vascular Biology, 32(12), 3050–3057. https://doi.org/10.1161/ATVBAHA.112.255190.
Wang, J., & Wang, H. (2017). Oxidative Stress in Pancreatic Beta Cell Regeneration. Oxidative medicine and cellular longevity, 2017, 1930261. https://doi.org/10.1155/2017/1930261
Watanabe, N., Endo, Y., FUJIMOTO, K., AOKI, H. (2006). Tempeh-like Fermented Soybean (GABA-tempeh) Has an Effective Influence on Lipid Metabolism in Rats. Journal of Oleo Science, 55(8), 391-396. https://doi.org/10.5650/jos.55.391
Watanabe, N., Fujimoto, K., & Aoki, H. (2007). Antioxidant activities of the water-soluble fraction in tempeh-like fermented soybean (GABA-tempeh). International journal of food sciences and nutrition, 58(8), 577–587. https://doi.org/10.1080/09637480701343846
Yang, Q., Graham, T. E., Mody, N., Preitner, F., Peroni, O. D., Zabolotny, J. M., Kotani, K., Quadro, L., & Kahn, B. B. (2005). Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature, 436(7049),356–362. https://doi.org/10.1038/nature03711
Yoshiaki, I., Saori, O., Takashi, N., Naoyuki, N. (2006). Oxidative stress induces phosphoenolpyruvate carboxykinase expression in H4IIE cells. Bioscience, Biotechnology, and Biochemistry, 70(9), 2191-2198. https://doi.org/10.1271/bbb.60135
Published
2021-05-11
How to Cite
Prasetyastuti, P., & Dian Setiawan Ghozali. (2021). The Effects of Soyferment-Tempeh on Lipid Profile, Retinol-Binding Protein 4 (RBP4), and Phosphoenolpyruvate Carboxykinase (PEPCK) Gene Expression in Type 2 Diabetic Mice. Indonesian Journal of Pharmacy, 32(2), 193-200. https://doi.org/10.22146/ijp.1354
Section
Research Article