Investigating the effects of compound WS090152 on non-alcoholic fatty liver in mice
10.16438/j.0513-4870.2016-0329
- VernacularTitle:化合物WS090152治疗小鼠单纯性脂肪肝的实验研究
- Author:
Ying ZHOU
1
;
Xiu-li LI
2
;
Qin YI
1
;
Xiao-lin ZHANG
1
;
Jin-ying TIAN
1
;
Dong-mei WANG
1
;
Song WU
1
;
Fei YE
1
Author Information
1. Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
2. Medical College of Chifeng University, Chifeng 024000, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
compound C28H35NO4Cl4;
non-alcoholic fatty liver;
protein tyrosine phosphatase 1B;
insulin resistance
- From:
Acta Pharmaceutica Sinica
2016;51(6):919-
- CountryChina
- Language:Chinese
-
Abstract:
To investigate the effects and the mechanism of compound WS090152 on non-alcoholic fatty liver (NAFL), the compound was administrated in C57BL/6J mice fed a high fat diet at 50 mg·kg-1 by lavage. The lipid accumulation in liver was determined by the content of hepatic triglyceride (TG) and the histological pathological analysis. The levels of body weight gain, serum total cholesterol (TC) and TG were measured to evaluate lipid metabolism. Insulin sensitivity was determined by glucose infusion rate (GIR) value in hyperinsulinemic-euglycemic clamp test. The expression of related proteins in liver was measured by Western blot. The effect on the target protein tyrosine phosphatase 1B (PTP1B) was assessed by the activity of recombinate human PTP1B in vitro, and by the expressions of PTP1B in vivo, respectively. The content of hepatic TG (P<0.05) and the pathological changes of the livers (P<0.001) were attenuated, insulin resistance was improved (P<0.01), and the levels of serum TC (P<0.01) and serum TG (P<0.05) were reduced by WS090152 treatment in the mice. The recombinant hPTP1B activity was significantly inhibited with IC50 value of 0.34 μmol·L-1; the expression of PTP1B was significantly downregulated, and the phosphorylation of its downstream insulin receptor (IR) and AKT was upregulated by WS090152 administration in the livers of NAFL mice. The expression of hepatic lipogenesis-related proteins-1c (SREBP-1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) was attenuated. These results suggest that compound WS090152 can ameliorate NAFL by increasing insulin sensitivity and decreasing hepatic lipogenesis probably through inhibition of PTP1B.
