TXNIP gene knockout ameliorates non-alcoholic fatty liver disease by regulating carbon flux of fatty acid synthesis and fatty acid oxidation
- VernacularTitle:TXNIP基因敲除通过调控脂肪酸合成的碳源通量及脂肪酸氧化而改善非酒精性脂肪肝
- Author:
Jun-nan ZHAO
1
;
Ai-yun LI
1
;
Wan-zhen SU
1
;
Xiao-xiao YIN
1
;
Tong LI
1
;
Xiang-ying JIAO
1
Author Information
- Publication Type:Journal Article
- Keywords: thioredoxin-interacting protein; non-alco-holic fatty liver disease; hepatic seatosis; fatty acid synthesis; carbon source flux; fatty acid oxidation
- From: Chinese Pharmacological Bulletin 2025;41(8):1524-1530
- CountryChina
- Language:Chinese
- Abstract: Aim To investigate the effect of thioredox-in-interacting protein(TXNIP)on non-alcoholic fatty liver disease(NAFLD).Methods Littermate male wild(WT)mice and TXNIP gene whole-body knock-out(KO)mice were randomly divided into two groups:(1)normal diet(ND)group,and(2)The high-fat group,which was fed a high-fat diet(HFD)containing 60％fat for 12 weeks.Serum lipid-related indexes,liver injury indicators and hepatic fat content were detected using commercial kits.The protein lev-els of TXNIP,SLC25A1,SLC13A5,ACLY,CPT1a and PPARα were detected by Western blot.The gene ex-pressions of SLC25A1,SLC13A5 and ACLY were de-tected by RT-PCR.Results High fat diet increased TXNIP protein expression in the liver tissue.Compared with WT-HFD mice,the biochemical indexes in the se-rum and the liver of KO-HFD mice were improved.There was no significant difference in mRNA and pro-tein levels of SLC25A1 between the four groups of mice.For SLC13A5 and ACLY,the mRNA and protein levels of WT-HFD mice were up-regulated compared with WT mice,and these alterations were significantly restored in KO-HFD mice.Besides,compared with WT mice,the protein expressions of the fatty acid oxidation-related protein PPARα and CPT1a proteins in WT-HFD mice decreased,while the protein expressions of PPARα and CPT1 a in KO-HFD mice were significantly enhanced.Conclusion TXNIP gene knockout can improve hepatic steatosis and delay the progression of NAFLD by inhibiting the carbon flux of fatty acid syn-thesis and promoting fatty acid oxidation.
