AdipoRon improves fibrosis liver function by regulating lipid metabolisms and remodeling macrophages polarization
10.19405/j.cnki.issn1000-1492.2025.04.010
- VernacularTitle:AdipoRon通过调节脂质代谢和重塑巨噬细胞表型改善肝纤维化的功能研究
- Author:
Haikun Wang
1
;
Ping Yao
1
;
Tao Yang
1
;
Lili Xi
1
Author Information
1. Dept of Gastroenterology，The First Affiliated Hospital of Xinjiang Medical University，Urumqi 830054
- Publication Type:Journal Article
- Keywords:
liver fibrosis;
adiponectin receptor agonist AdipoRon;
liver function;
lipid metabolism;
macrophage polarization;
CCl4 -induced liver fibrosis mouse model
- From:
Acta Universitatis Medicinalis Anhui
2025;60(4):656-663
- CountryChina
- Language:Chinese
-
Abstract:
Objective : To investigate the role of AdipoRon, an adiponectin receptor agonist, in treatment of carbon tetrachloride(CCl4) induced liver fibrosis mice model and the mechanisms.
Methods : Forty mice were randomly divided into control group, model group, L-AdipoRon group and H-AdipoRon group, with 10 mice in each group. Hepatic fibrosis was induced by intraperitoneal injection of CCl4solution. The mice in L-and H-AdipoRon groups were given 100 mg/kg and 200 mg/kg AdipoRon by gavage, respectively. The activities of serum aspartate aminotransferase(AST) and alanine aminotransferase(ALT) were detected by biochemical method. Liver histopathological changes and fibrosis were detected by HE staining, Masson staining and Sirius scarlet stain. The protein expression levels of Collagen I, α-smooth muscle actin(α-SMA), matrix metalloproteinase 1(MMP-1) and matrix metalloproteinase inhibitor 1(TIMP-1) in mice liver were detected by Western blot. Lipid deposition in liver were detected by oil red O staining. The percentage(%) of CD68+ iNOS+ positive M1-type macrophages in the liver were detected by immunofluorescence. The expression levels of fatty acid synthetase(Fasn), stearoyl-CoA desaturase 1(Scd1), fatty acid transporter(Cd36), peroxissome proliferator activated receptor-α(Pparα) and carnitine palmitoyl transferase 1α(Cpt1α) in mice liver tissues, as well as M1 macrophage-related genes interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) and M2 macrophage-related genes arginase 1(Arg1), Chil3 chitinase-like 3(Ym-1) were detected by RT-qPCR assay.
Results :Compared with model group, in low-dose AdipoRon group and high-dose AdipoRon group, serum ALT and AST activities significantly decreased(P<0.05); liver tissues structure were damaged, liver cells degeneration and inflammatory cells infiltration were improved; collagen fiber deposition was also significantly reduced; the relative expression levels of Collagen I, α-SMA and TIMP-1 proteins were significantly down-regulated(P<0.05), while the relative expression levels of MMP-1 protein were significantly up-regulated(P<0.05); the lipid droplets deposition in livers were significantly reduced. The relative Fasn, Scd1 and Cd36 mRNA expression levels in liver tissues were significantly down-regulated(P<0.05), and the relative Pparα and Cpt1α mRNA expression levels were significantly up-regulated(P<0.05); the percentage(%) of CD68+ iNOS+ positive M1-type macrophages significantly decreased(P<0.05); the relative IL-6 and TNF-α mRNA expression levels significantly decreased(P<0.05), the relative Arg1 and Ym-1 mRNA expression levels were significantly up-regulated(P<0.05). In addition, the improvement effects of high-dose AdipoRon group were better than those of low-dose AdipoRon group(P<0.05).
Conclusion :AdipoRon can improve the disorder of lipid metabolisms, inhibit the M1 type macrophages polarization, and improve the liver fibrosis in CCl4-induced liver fibrosis mice model.
- Full text:2026012609520872855AdipoRon通过调节脂...表型改善肝纤维化的功能研究_王海昆.pdf
