Role and mechanism of indole-3-propionic acid improving metabolic associated fatty liver disease by regulating adipose tissue metabolism

Yu YAO; Pengfei HOU; Min ZHOU; Hedong LANG; Minghua LIU; Long YI; Mantian MI

doi:10.16016/j.2097-0927.202309045

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Role and mechanism of indole-3-propionic acid improving metabolic associated fatty liver disease by regulating adipose tissue metabolism

Public Health and Preventive Medicine | 更新时间：2026-01-09

- Role and mechanism of indole-3-propionic acid improving metabolic associated fatty liver disease by regulating adipose tissue metabolism
- Journal of Army Medical University Vol. 46, Issue 9, Pages: 919-927(2024)
- 作者机构：
  
  400038 重庆，陆军军医大学(第三军医大学)军事预防医学系营养与食品安全研究中心，重庆市医学营养研究中心，营养与健康重庆市重点实验室
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(82173506)
- DOI：10.16016/j.2097-0927.202309045
  CLC： R591.5;R575.5;R977.4
- Received：11 September 2023，
  
  Revised：2023-12-03，
  
  Published：15 May 2024
- 稿件说明：
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Yu YAO, Pengfei HOU, Min ZHOU, et al. Role and mechanism of indole-3-propionic acid improving metabolic associated fatty liver disease by regulating adipose tissue metabolism[J]. Journal of Army Medical University, 2024, 46(9): 919-927.
DOI：

Yu YAO, Pengfei HOU, Min ZHOU, et al. Role and mechanism of indole-3-propionic acid improving metabolic associated fatty liver disease by regulating adipose tissue metabolism[J]. Journal of Army Medical University, 2024, 46(9): 919-927. DOI： 10.16016/j.2097-0927.202309045.

摘要

目的

探索吲哚-3-丙酸(indole-3-propionic acid，IPA)在高脂饮食诱导代谢相关脂肪性肝病(metabolic associated fatty liver disease，MAFLD)发生发展中的作用，揭示脂肪组织代谢在其中的作用及相关机制。

方法

建立高脂饮食(high-fat diet，HFD)喂养诱导的MAFLD动物模型，6~7周龄的雄性C57BL/6J小鼠按随机数字表法分为3组，即对照组(CON)、高脂饮食组(HFD)、高脂+IPA干预组(HFD+IPA)。CON组以对照饲料喂养，HFD组和HFD+IPA组均以60%高脂饲料喂养，实验周期为12周，第7周开始HFD+IPA组以20 mg/(kg·d)IPA灌胃6周。每周监测各组小鼠体质量与摄食量。干预结束后使用动物体成分分析仪检测小鼠体成分。小鼠处死后，HE染色观察肝脏和脂肪组织形态学和结构变化，全自动血生化仪和生化试剂盒检测血清及肝脏和脂肪组织中脂代谢相关指标，qRT-PCR检测脂代谢和炎性相关基因mRNA的表达。

结果

与CON组相比，HFD组小鼠体质量和体脂肪比例显著增加，肝脏出现明显的脂质沉积，血清丙氨酸氨基转移酶、天冬氨酸氨基转氨酶以及肝脏甘油三酯和总胆固醇水平显著升高(

0.05)，肝组织脂肪酸转运分子

36的mRNA水平明显升高(

0.05)，IPA干预显著逆转了上述变化(

0.05)。IPA干预能够显著抑制高脂饮食诱导的内脏和棕色脂肪细胞增大，降低内脏脂肪组织(visceral adipose tissue，VAT)和血清中游离脂肪酸含量(

0.05)，增加VAT脂解基因(

HSL

、

CGI

58)和棕色化(

Cidea

、

5、

UCP

1、

Prdm

16)以及棕色脂肪组织(brown adipose tissue，BAT)脂肪酸β氧化(

Cpt

、

PPARα

)相关基因的mRNA表达水平(

0.05)，同时降低VAT炎性因子

TNF

以及BAT中

TNF

、

-1

、

CXCL

1、

CCL

2的mRNA表达水平(

0.05)。

结论

IPA可以改善高脂饮食诱导的MAFLD的发生，其机制可能与调节白色和棕色脂肪组织结构、代谢功能及炎性相关基因的表达有关。

Abstract

Objective

To explore the role of indole-3-propionic acid (IPA) in the pathogenesis of metabolic associated fatty liver disease (MAFLD) induced by high-fat diet (HFD) in order to reveal the role and related mechanism of adipose tissue metabolism in the process.

Methods

A mouse model of MAFLD was induced by HFD. Male C57BL/6J mice (6~7 weeks old) were randomly divided into control group (CON)

HFD group

and HFD+IPA intervention group (HFD+IPA). The CON group was fed with control diet

and the HFD group and HFD+IPA group were fed with 60% of high-fat diet. The experiment period was 12 weeks

and IPA was administered at 20 mg/(kg·d) for 6 weeks starting from the 7th week. The body weight and food intake of each group were monitored weekly. After the intervention

the body composition of mice was detected by animal body composition analyzer. After the mice were euthanized

the morphological and structural changes in the liver and adipose tissues were observed by HE staining

the indicators relevant to lipid metabolism in the serum

liver and adipose tissues were detected by automatic blood biochemical analyzer and biochemical kits

and the mRNA expression changes of lipid metabolism and inflammation related genes were detected by qRT-PCR.

Results

Compared with the CON group

the HFD group had significantly increased body weight and body fat percentage

obvious lipid deposition in the liver

obviously elevated serum alanine aminotransferase

aspartate aminotransferase

liver triglyceride and total cholesterol levels (

0.05)

and raised mRNA levels of liver fatty acid transporter

36 (

0.05)

while IPA intervention significantly reversed the above changes (

0.05). IPA intervention significantly inhibited the HFD-induced enlargement of visceral and brown fat cells

reduced the content of visceral adipose tissue (VAT) and serum level of free fatty acids (

0.05)

and increased the mRNA expression levels of VAT lipolysis (HSL

CGI58)

browning genes (

Cidea

UCP

Prdm

16) (

0.05)

as well as those of brown adipose tissue (BAT) lipo

lysis (

HSL

ATGL

) and fatty acid beta oxidation (

Cpt

PPARα

) genes (

0.05). Meanwhile

the mRNA levels of

TNF

-1

CXCL

1 and

CCL

2 in VAT and BAT were decreased after IPA intervention (

0.05).

Conclusion

IPA can improve the occurrence of MAFLD induced by HFD

and its mechanism may be closely associated with its regulation of BAT and VAT morphology

and the mRNA expression of metabolic function and inflammation related genes.

关键词

Keywords

references

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