S-Equol improves type 2 diabetes mellitus combined with nonalcoholic fatty liver disease by regulating SREBP pathway and PPARγ in rats

Zhe XU; Xiangmin NI; Shuo LI; Guiming ZHANG; Hanqiang CUI; Jian WANG

doi:10.16016/j.2097-0927.202206081

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S-Equol improves type 2 diabetes mellitus combined with nonalcoholic fatty liver disease by regulating SREBP pathway and PPARγ in rats

Basic Medicine | 更新时间：2026-01-09

- S-Equol improves type 2 diabetes mellitus combined with nonalcoholic fatty liver disease by regulating SREBP pathway and PPARγ in rats
- Journal of Army Medical University Vol. 44, Issue 22, Pages: 2266-2274(2022)
- 作者机构：
  
  400037 重庆，陆军军医大学(第三军医大学)第二附属医院营养科
- 作者简介：
- 基金信息：
  
  the General Program of National Nature Science Foundation of China(81973040);the National Natural Science Foundation for Young Scholars of China(81602855)
- DOI：10.16016/j.2097-0927.202206081
  CLC： R151.3;R575.5;R587.1
- Received：12 June 2022，
  
  Revised：2022-07-26，
  
  Published：30 November 2022
- 稿件说明：
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Zhe XU, Xiangmin NI, Shuo LI, et al. S-Equol improves type 2 diabetes mellitus combined with nonalcoholic fatty liver disease by regulating SREBP pathway and PPARγ in rats[J]. Journal of Army Medical University, 2022, 44(22): 2266-2274.
DOI：

Zhe XU, Xiangmin NI, Shuo LI, et al. S-Equol improves type 2 diabetes mellitus combined with nonalcoholic fatty liver disease by regulating SREBP pathway and PPARγ in rats[J]. Journal of Army Medical University, 2022, 44(22): 2266-2274. DOI： 10.16016/j.2097-0927.202206081.

摘要

目的

分析S-雌马酚(S-Equol)对2型糖尿病(type 2 diabetes mellitus

T2DM)合并非酒精性脂肪肝(non-alcoholic fatty liver disease

NAFLD)大鼠模型糖脂代谢的影响。

方法

选取6周龄雄性SD大鼠50只，适应性饲养1周，随机分为对照组(

=10)和建模组(

=40)。给予建模组大鼠高脂高糖饮食联合腹腔注射链尿佐菌素(streptozocin

STZ)构建2型糖尿病模型。空腹血糖(fasting blood-glucose

FBG)

11.1 mmol/L的大鼠随机分为模型组(

=9)，S-Equol低剂量组(20 mg·kg

-1

·d

-1

=9)、中剂量组(40 mg·kg

-1

·d

-1

=8)和高剂量组(80 mg·kg

-1

·d

-1

=8)。干预满12周后，检测各组大鼠血清总胆固醇(TC)、甘油三酯(TG)、血糖(FBG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、总胆红素(

TBIL)、直接胆红素(DBIL)、总蛋白(TP)、白蛋白(Alb)、球蛋白(Glb)。采用ELISA法检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)以及肝脏白介素1β(IL-1β)、白介素6(IL-6)和肿瘤坏死因子-α(TNF-α)。采用Western blot和RT-qPCR法检测肝组织中与脂质代谢相关的过氧化物酶体增殖物激活受体γ(peroxisome proliferator-activated receptor gamma

PPARγ)，乙酰辅酶a羧化酶(acetyl-CoA carboxylase

ACC)，固醇调节元件结合蛋白-1(sterol regulatory element binding protein-1

SREBP-1)和脂肪酸合成酶(fatty acid synthetase

Fasn)表达水平。

结果

与模型组比较，S-Equol低剂量组胰岛素抵抗水平显著降低(

0.05)，S-Equol中剂量组胰岛素分泌水平显著升高(

0.05)，S-Equol低、高剂量组FBG水平显著降低(

0.05)，S-Equol低剂量组肝指数、血清白球比(A/G)和LDL显著降低(

0.05)，S-Equol中剂量组血清DBIL和ALT显著降低(

0.05)；S-Equol低、中、高剂量组肝脏组织学形态均改善，肝脏脂质沉积面积显著降低(

0.05)，S-Equol中、高剂量组肝组织炎症水平显著降低(

0.05)；Western blot结果显示，中、高剂量的S-Equol干预使大鼠肝组织中PPARγ和ACC的表达显著下调(

0.05)；RT-qPCR结果显示S-Equol的干预使大鼠肝组织中ACC、SREBP-1、Fasn和PPARγ转录水平显著降低(

0.05)。

结论

S-Equol能降低T2DM合并NAFLD大鼠的肝脏脂质沉积、脂质代谢相关分子表达和炎症水平，其机制可能与调节SREBP通路和PPARγ分子表达有关。

Abstract

Objective

To analyze the effects of S-Equol on glucose and lipid metabolism in rats with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD).

Methods

Fifty SD rats aged 6 weeks were randomly divided into the control group (

=10) and the modeling group (

=40) after 1 week's adaptive feed. The modeling group was given high-fat and high-sugar diet combined with streptozotocin (STZ) intrabdominal injection to construct T2DM model. Rats whose fasting blood-glucose (FBG) level was greater than 11.1 mmol/L were randomly divided into the 4 groups: the model group

the S-Equol low-dose group(20 mg·kg

-1

·d

-1

)

the S-Equol medium-dose group(40 mg·kg

-1

·d

-1

)and the S-Equol high-dose group(80 mg·kg

-1

·d

-1

). After 12 weeks of intervention

the level of serum total cholesterol (TC)

triglyceride (TG)

FBG

high density lipoprotein (HDL)

low density lipoprotein (LDL)

total bilirubin (TBIL)

direct bilirubin (DBIL)

total protein (TP)

albumin (Alb) and globulin (Glb) were detected. Serum alanine aminotransferase (ALT)

aspartate aminotransferase (AST) and liver interleukin-1β (IL-1β)

interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected by ELISA. Peroxisome proliferator-activated receptor gamma (PPARγ)

acetyl-CoA carboxylase (ACC)

sterol regulatory element binding protein-1 (SREBP-1) and fatty acid synthetase (Fasn) expression levels related to lipid metabolism were detected by Western blotting and RT-qPCR.

Results

Compared with the model group

the S-Equol low-dose group had significantly decreased levels of insulin resistance (

0.05)

the S-Equol medium-dose group had significantly decreased levels of insulin secretion (

0.05)

and the S-Equol low-and high-dose groups had obviously decreased levels of FBG (

0.05); The S-Equol low-dose group had significantly decreased liver index

albumin/globulin ratio (A/G) and LDL (

0.05)

and the S-Equol medium-dose group had significantly decreased DBIL and ALT (

0.05). Compared with the model group

the histological morphology of liver in the S-Equol low-

medium- and high-dose groups improved and the area of liver lipid deposition decreased obviously (

0.05)

and the S-Equol medium-dose group and the high-dose group had reduced liver inflammation (

0.05). The results of Western blotting showed the expression of PPARγ and ACC in liver tissue of rats was significantly down-regulated by medium- and high-dose S-Equol intervention (

0.05). The results of RT-qPCR showed that S-Equol intervention significantly could reduc

e the transcription levels of ACC

SREBP-1

Fasn and PPARγ in liver tissue of rats (

0.05).

Conclusion

The intervention of S-Equol can reduce liver lipid deposition

lipid metabolism-related molecule expression and inflammation in T2DM rats with NAFLD

and the mechanism may be related to regulating SREBP pathway and PPARγ expression.

关键词

Keywords

references

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