题  目: Obesity and Fatty Liver

主讲人:李小英  研究员

主持人:翁杰敏  教  授

时  间:10月9日13:30

地  点:闵行校区生科院534报告厅

 

报告人简介：

李小英，上海交通大学医学院附属瑞金医院内分泌代谢科教授、主任医师、博士生导师，上海市内分泌代谢病研究所副所长。1983年毕业于衡阳医学院，获学士学位；1997年获第三军医大学硕士学位；1996年毕业于上海第二医科大学，获博士学位。1998-2003年先后在美国Baylor医学院、加拿大McGill大学和UBC大学做博士后研究，2009年入选上海市优秀学科带头人，主要从事糖尿病发病机制和性腺疾病研究。发表SCI论文58篇，撰写专著3部。担任《Journal of Diabetes》杂志副主编，《中华内分泌代谢杂志》、《中华糖尿病杂志》、《中国糖尿病杂志》编委，兼中华医学会糖尿病学分会委员，上海市糖尿病学会副主任委员。

 

报告内容简介：

Fatty liver is prevalent in obese population. Hepatosteatosis is characterized by an aberrant accumulation of triglycerides in the liver; however, the factors that drive obesity-induced fatty liver remain largely unknown. Here, we demonstrated that the secreted cell adhesion protein periostin is markedly upregulated in livers of obese rodents and humans. Notably, overexpression of periostin in the livers of WT mice promoted hepatic steatosis and hypertriglyceridemia. Conversely, both genetic ablation of periostin and administration of a periostin-neutralizing antibody dramatically improved hepatosteatosis and hypertriglyceridemia in obese mice. Overexpression of periostin resulted in reduced expression of peroxisome proliferator–activated receptor α (PPARα), a master regulator of fatty acid oxidation, and activation of the JNK signaling pathway. In mouse primary hepatocytes, inhibition of α6β4 integrin prevented activation of JNK and suppression of PPARα in response to periostin. Periostin-dependent activation of JNK resulted in activation of c-Jun, which prevented RORα binding and transactional activation at the Ppara promoter.

Together, these results identify a periostin-dependent pathway that mediates obesity-induced hepatosteatosis.