常永生课题组在《J Hepatol》 杂志发表研究论文“Sirt1 mediates the effect of the heme oxygenase inducer, cobalt protoporphyrin, on ameliorating liver metabolic damage caused by a high-fat diet （2015）”。

       为研究HO-1在肝脏脂代谢中的作用，中国医学科学院基础医学研究所，“医学分子生物学国家重点实验室”的常永生课题组揭示了Sirt1介导CoPP改善高脂饮食造成的肝脏损伤的作用。

      【摘要】：Background & Aims: Heme oxygenase 1 (HO-1)-mediated increases in adiponectin, ameliorate the deleterious effects of obesity and metabolic syndrome; however, the effect of HO-1 on hepatic lipid metabolism remains elusive. The aim of this study is to evaluate the role of HO-1 in hepatic lipid metabolism. Methods: Functional studies were performed using C57BL/6J(WT) mice and Sirt1 liver specific mutant (Sirt1-deficient) mice. The molecular mechanism was explored in primary hepatocytes and mouse liver. Results: Chronic exposure to high-fat diet (HFD) induced hepatic steatosis in WT mice. Treatment of WT mice on HFD with cobaltprotoporphyrin (CoPP), an inducer of HO-1 activity, decreased body weight and visceral fat content, reduced intracellular hepatic triglyceride and serum total cholesterol concentrations, and decreased liver lipid droplet formation. Compared with WT mice, the administration of CoPP to Sirt1-deficient mice on HFD increased visceral fat content, and slightly promoted liver lipid droplet formation. CoPP improved glucose tolerance and insulin sensitivity in WT mice on HFD, but compromised insulin sensitivity in Sirt1-deficient mice on HFD. Furthermore, CoPP-induced Sirt1 expression and decreased sterol regulatory element binding protein 1c (SREBP-1c) expression in WT mice on HFD. However, CoPP promoted SREBP-1c expression in Sirt1-deficient hepatocytes, which was reversed by a proteintyrosine phosphatase 1b inhibitor. Additionally, while the administration of CoPP to WT mice on HFD improved antioxidant and anti-inflammatory states, these CoPP-mediated effects were abolished in Sirt1-deficient mice. Conclusions: Sirt1 mediates the effect of CoPP on amelioratingliver metabolic damage caused by HFD.

       相关结果已发表于《J Hepatol》 杂志（2015，63(3):713-21.），其作者为常永生课题组博士研究生刘晓军，高永，重点室刘晓军，方福德，常永生副研究员，研究员是本文的通讯作者。该研究工作得到了以下基金的支持：973，国自然。

      医学分子生物学国家重点实验室