Role and mechanism of indole-3-propionic acid improving metabolic associated fatty liver disease by regulating adipose tissue metabolism
10.16016/j.2097-0927.202309045
- VernacularTitle:吲哚-3-丙酸通过调节脂肪组织代谢改善高脂饮食诱导代谢相关脂肪性肝病的作用及机制研究
- Author:
Yu YAO
1
;
Pengfei HOU
;
Min ZHOU
;
Hedong LANG
;
Minghua LIU
;
Long YI
;
Mantian MI
Author Information
1. 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
- Keywords:
indole-3-propionic acid;
metabolic related fatty liver disease;
liver;
visceral adipose tissue;
brown adipose tissue
- From:
Journal of Army Medical University
2024;46(9):919-927
- CountryChina
- Language:Chinese
-
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,l iver 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(P<0.05),and raised mRNA levels of liver fatty acid transporter CD36(P<0.05),while IPA intervention significantly reversed the above changes(P<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(P<0.05),and increased the mRNA expression levels of VAT lipolysis(HSL,CGI58),browning genes(Cidea,ND5,UCP1,Prdm16)(P<0.05),as well as those of brown adipose tissue(BAT)lipolysis(HSL,ATGL)and fatty acid beta oxidation(Cpt1a,PPARα)genes(P<0.05).Meanwhile,the mRNA levels of TNF-α,IL-1β,CXCL1 and CCL2 in VAT and BAT were decreased after IPA intervention(P<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.