Effect of Sodium Butyrate on Infiltrated Treg and Th17 Proportion in Adipose Tissues and Insulin Sensitivity in Type 2 Diabetic Mice

doi:10.3870/j.issn.1672-8009.2025.06.005

Abstract

Abstract: Objective To explore the immunological mechanisms of sodium butyrate on improving Type 2 diabetic mouse model’s insulin sensitivity. Methods Type 2 diabetic mouse model was established by feeding with a high-fat/high-sucrose diet combined with streptozotocin induction.Thirty male C57BL/6 mice were divided into three groups:control group,model group,model+sodium butyrate group,10 mice in each group.The values of glucose tolerance test and insulin tolerance test were measured.The proportion of infiltrated regulatory T cells(Treg)(%)and T helper type 17(Th17)(%)in mice peripheral blood and adipose tissues were measured by flow cytometry.Western blotting was used to determine the relative expression levels of p-mTOR,mTOR,p-p70S6K and p70S6K in infiltrated Treg and Th17 cells in adipose tissues. Results Glucose tolerance test results have shown that compared with control group,in model+sodium butyrate group blood glucose levels increased at 20 min(P<0.05);there was no statistically significant difference in blood glucose at subsequent time points(P>0.05).Insulin tolerance test results have shown that there was no significant difference in blood glucose levels in model+sodium butyrate group at any time points(P>0.05).Compared with those in the control group,the percentage(%)of infiltrating Th17 cells in peripheral blood and adipose tissues was increased in the model group(P<0.05),and the percentage(%)of infiltrating Treg cells was decreased(P<0.05),and the relative expression levels of p-mTOR and p-p70S6K in infiltrated Treg cells and Th17 cells in adipose tissues were increased(P<0.05).Compared with the model group,the model+sodium butyrate group significantly reversed the above indicator values(P<0.05). Conclusion Sodium butyrate treatment could inhibit the activation levels of mTOR/p70S6K signaling pathway,regulate the numbers of Treg cells and Th17 cells in peripheral blood and adipose tissues,and improve insulin sensitivity in type 2 diabetes mice model.

Key words: type 2 diabetes mellitus, insulin sensitivity, sodium butyrate, regulatory T cells, T helper type 17 cells

CLC Number:

R587.1
R576

WANG Siyao, GAO Jing, ZHANG Chunxue, LUO Li, JIN Jin. Effect of Sodium Butyrate on Infiltrated Treg and Th17 Proportion in Adipose Tissues and Insulin Sensitivity in Type 2 Diabetic Mice[J]. Journal of Medical Molecular Biology, 2025, 22(6): 563-570.

References

[1] SUN H,SAEEDI P,KARURANGA S,et al.IDFdiabetes atlas:global,regional and country-level diabetes prevalence estimates for 2021 and projections for 2045[J].Diabetes Res Clin Pract,2022,183:109119.
[2] TINAJERO M G,MALIK V S.An update on the epidemiology of type 2 diabetes:a global perspective[J].Endocrinol Metab Clin North Am,2021,50(3):337-355.
[3] ZHOU Z,SUN B,YU D,et al.Gut microbiota:an important player in type 2 diabetes mellitus[J].Front Cell Infect Microbiol,2022,12:834485.
[4] 闫芬芬,李娜,李柏良,等.益生菌对2型糖尿病影响的研究进展[J].食品科学,2019,40(21):295-302.
[5] RAHMAN M M,ISLAM F,-OR-RASHID M H,et al.The gut microbiota(microbiome)in cardiovascular disease and its therapeutic regulation[J].Front Cell Infect Microbiol,2022,12:903570.
[6] CHEN Y,ZHOU J,WANG L.Role and mechanism of gut microbiota in human disease[J].Front Cell Infect Microbiol,2021,11:625913.
[7] WU J,YANG K,FAN H,et al.Targeting the gut microbiota and its metabolites for type 2 diabetes mellitus[J].Front Endocrinol(Lausanne),2023,14:1114424.
[8] ZHANG D,JIAN Y P,ZHANG Y N,et al.Short-chain fatty acids in diseases[J].Cell Commun Signal,2023,21(1):212.
[9] MCMURDIE P J,STOEVA M K,JUSTICE N,et al.Increased circulating butyrate and ursodeoxycholate during probiotic intervention in humans with type 2 diabetes[J].BMC Microbiol,2022,22(1):19.
[10] DARYABOR G,ATASHZAR M R,KABELITZ D,et al.The effects of type 2 diabetes mellitus on Oorgan metabolism and the immune system[J].Front Immunol,2020,11:1582.
[11] ZHANG S,GANG X,YANG S,et al.The alterations in and the role of the Th17/Treg balance in metabolic diseases[J].Front Immunol,2021,12:678355.
[12] ZI C,HE L,YAO H,et al.Changes of Th17 cells,regulatory T cells,Treg/Th17,IL-17 and IL-10 in patients with type 2 diabetes mellitus:a systematic review and meta-analysis[J].Endocrine,2022,76(2):263-272.
[13] WU D,WONG C K,HAN J M,et al.T reg-specific insulin receptor deletion prevents diet-induced and age-associated metabolic syndrome[J].J Exp Med,2020,217(8):e20191542.
[14] FURMAN B L.Streptozotocin-Induced Diabetic models in mice and rats[J].Curr Protoc,2021,1(4):e78.
[15] HUANG F C,HUANG S C.The pivotal role of aryl hydrocarbon receptor-regulated tight junction proteins and innate immunity on the synergistic effects of postbiotic butyrate and active vitamin D3 to defense against microbial invasion in salmonella colitis[J].Nutrients,2023,15(2):305.
[16] LEE Y S,OLEFSKY J.Chronic tissue inflammation and metabolic disease[J].Genes Dev,2021,35(5-6):307-328.
[17] YING W,FU W,LEE Y S,et al.The role of macrophages in obesity-associated islet inflammation and β-cell abnormalities[J].Nat Rev Endocrinol,2020,16(2):81-90.
[18] ADANE T,MELKU M,WORKU Y B,et al.The Association between neutrophil-to-lymphocyte ratio and glycemic control in type 2 diabetes mellitus:a systematic review and meta-analysis[J].J Diabetes Res,2023,2023:3117396.
[19] GUZMAN-FLORES J M,RAMIREZ-EMILIANO J,PEREZ-VAZQUEZ V,et al.Th17 and regulatory T cells in patients with different time of progression of type 2 diabetes mellitus[J].Cent Eur J Immunol,2020,45(1):29-36.
[20] ZHANG S,GANG X,YANG S,et al.The alterations in and the role of the Th17/Treg balance in metabolic diseases[J].Front Immunol,2021,12:678355.
[21] YANG W,CHEN X,HU H.CD4+ T-cell differentiation in vitro[J].Methods Mol Biol,2020,2111:91-99.
[22] KUMAR R,THEISS A L,VENUPRASAD K.RORγt protein modifications and IL-17-mediated inflammation[J].Trends Immunol,2021,42(11):1037-1050.
[23] XU Q,ZHANG X,LI T,et al.Exenatide regulates Th17/Treg balance via PI3 K/Akt/FoxO1 pathway in db/db mice[J].Mol Med,2022,28(1):144.
[24] FAN Y,PEDERSEN O.Gut microbiota in human metabolic health and disease[J].Nat Rev Microbiol,2021,19(1):55-71.
[25] LIANG C,ZHOU X H,JIAO Y H,et al.Ligilactobacillus salivarius LCK11 prevents obesity by promoting PYY secretion to inhibit appetite and regulating gut microbiota in C57BL/6 J mice[J].Mol Nutr Food Res,2021,65(17):e2100136.
[26] CALVO-BARREIRO L,ZHANG L,ABDEL-RAHMAN S A,et al.Gut microbial-derived metabolites as immune modulators of T helper 17 and regulatory T cells[J].Int J Mol Sci,2023,24(2):1806.
[27] ASLAMY A,WOOD A C,JENSEN E T,et al.Increased plasma branched short-chain fatty acids and improved glucose homeostasis:the microbiome and insulin longitudinal evaluation study(MILES)[J].Diabetes,2024,73(3):385-390.
[28] HE L,ZHONG Z,WEN S,et al.Gut microbiota-derived butyrate restores impaired regulatory T cells in patients with AChR myasthenia gravis via mTOR-mediated autophagy[J].Cell Commun Signal,2024,22(1):215.