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(S)YS-51, a novel isoquinoline alkaloid, attenuates obesity-associated non-alcoholic fatty liver disease in mice by suppressing lipogenesis, inflammation and coagulation.

Abstract：

:Obesity-associated non-alcoholic fatty liver disease (NAFLD) increases coagulation and inflammation. We hypothesized that (S)YS-51, an agent found to be beneficial in animal models of sepsis, may reduce NAFLD in high-fat diet (HFD) mice by reducing coagulation and inflammation. C57BL/6 mice were fed either a chow diet or HFD and each was supplemented with or without (S)YS-51 (10mg/kg, daily, i.p.) for 16 weeks. The results showed that HFD caused significant increases in lipogenesis [CD36, fatty acid synthase (FAS) and sterol response element binding protein (SREBP)-1c mRNA and protein], inflammation [monocyte chemotactic protein (MCP)-1, tumor necrosis factor (TNF)-α, intercellular cell adhesion molecule-1 (ICAM-1), TGF-β, and procollagen type 1 mRNA, macrophage infiltration] and coagulation [tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) mRNA and thrombin antithrombin complex (TAT)] in the liver, adipose tissue and serum, which were significantly reduced by (S)YS-51. These results of (S)YS-51 were accompanied by significant reduction of weight gain, liver size, hepatic steatosis and fibrosis, blood cholesterol, hepatic triglyceride, and macrophage infiltration and inflammatory cytokines in adipose tissue without affecting food intake in HFD mice. Interestingly, (S)YS-51 increased SIRT1 mRNA and protein and AMPK expression in the liver of HFD mice by increasing both NAD(+)/NADH ratio and LKB1 phosphorylation. In HepG2 cells, (S)YS-51 activated SIRT1 followed by AMPK. Finally, (S)YS-51 improved glucose tolerance and insulin resistance in HFD mice. We concluded that (S)YS-51 attenuates NAFLD and insulin resistance in HFD mice by, at least, activation of SIRT1/AMPK signals. Thus, (S)YS-51 may be beneficial in NAFLD treatment.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Park EJ,Kim YM,Kim HJ,Jang SY,Oh MH,Lee DH,Chang KC

doi

10.1016/j.ejphar.2016.06.040

subject

Has Abstract

pub_date

2016-10-05 00:00:00

pages

200-209

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(16)30399-5

journal_volume

788

pub_type

杂志文章

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(S)YS-51, a novel isoquinoline alkaloid, attenuates obesity-associated non-alcoholic fatty liver disease in mice by suppressing lipogenesis, inflammation and coagulation.