【摘 要】
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The excess deposition of underlying extracellular matrix(ECM)in adipose tissue is defined as adipose tissue fibrosis that is a major contributor to metabolic disorder such as obesity and type 2 diabetes.Anti-fibrosis therapy has received much attention in
【机 构】
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School of Pharmacy,Second Military Medical University/Naval Medical University,Shanghai 200433,China
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The excess deposition of underlying extracellular matrix(ECM)in adipose tissue is defined as adipose tissue fibrosis that is a major contributor to metabolic disorder such as obesity and type 2 diabetes.Anti-fibrosis therapy has received much attention in the treatment of metabolic disorders.Orosomucoid(ORM)is an acute-phase protein mainly produced by liver,which is also an adipokine.In this study,we investigated the effects of ORM on adipose tissue fibrosis and the potential mechanisms.We showed that ORM 1-deficient mice exhibited an obese phenotype,manifested by excessive collagen deposition in adipose tissues and elevated expression of ECM regulators such as metalloproteinases(MMP-2,MMP-13,MMP-14)and tissue inhibitors of metalloproteinases(TIMP-1,TIMP-2,TIMP-3).Administration of exogenous ORM(50mg·kg-1·d-1,ip)for 7 consecutive days in high-fat diet(HFD)-fed mice and leptin receptor(LepR)-deficient db/db mice attenuated these abnormal expressions.Meanwhile,ORM administration stimulated AMP-activated protein kinase(AMPK)phosphorylation and decreased transforming growth factor-β1(TGF-β1)level in adipose tissues of the mice.In TGF-β1-treated 3T3-L1 fibroblasts,ORM(10 μg/mL)improved the impaired expression profiles of fibrosis-related genes,whereas a selective AMPK inhibitor dorsomorphin(1 μmol/mL)abolished these effects.Together,our results suggest that ORM exerts a direct anti-fibrosis effect in adipose tissue via AMPK activation.ORM is expected to become a novel target for the treatment of adipose tissue fibrosis.
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