5月3日，国际学术期刊Diabetes 在线发表了中国科学院上海生命科学研究院营养科学研究所郭非凡组的研究论文：A novel function of hepatic FOG2 in insulin sensitivity and lipid metabolism via peroxisome proliferator-Activated Receptor Alpha。该研究发现肝脏FOG2通过影响ppARα表达调节胰岛素敏感性和肝脏脂质代谢的重要作用，为二型糖尿病以及脂肪肝的发病机制及治疗提供了新的理论基础和思路。

近年来，随着生活方式和饮食结构的改变，二型糖尿病和非酒精性脂肪肝的发病率逐年增加，二型糖尿病和非酒精性脂肪肝的发生会导致多种代谢性疾病的产生，严重�：θ死嗟纳】�。胰岛素抵抗是二型糖尿病的重要病理特征，而胰岛素抵抗又和脂质代谢的异常密不可分。目前，关于胰岛素抵抗的具体分子机制并不十分清楚。FOG2作为一个重要的转录共调节因子，其在血管生成、发育方面发挥着重要的生物学作用，然而其在胰岛素敏感性和脂肪肝方面的作用目前还从未被报道。

郭非凡研究组发现，FOG2在db/db小鼠（胰岛素抵抗模型）肝脏中表达显著上调，通过尾静脉注射腺病毒技术向db/db小鼠中注射FOG2干扰腺病毒可以显著缓解小鼠的胰岛素抵抗，提高胰岛素敏感性，而在野生型小鼠中注射过表达FOG2腺病毒又可以显著降低小鼠的胰岛素敏感性。进一步的研究表明，野生型小鼠中降低FOG2会导致肝脏脂质的显著积累，而过表达FOG2可以显著减少肝脏脂质的积累。深入的机制探索发现，FOG2是通过NR2F2介导，影响ppARα的表达来影响小鼠的胰岛素敏感性及肝脏脂质代谢过程。

该研究证明了FOG2在调节胰岛素敏感性和脂质代谢方面的重要作用，有助于加深人们对于二型糖尿病和脂肪肝发病机制的理解，为治疗二型糖尿病和脂肪肝提供药物靶点。

该研究工作得到了武汉大学教授刘勇的支持和帮助，并获得国家自然科学基金、科技部以及中科院等科研基金的支持。

原文摘要：

A novel function of hepatic FOG2 in insulin sensitivity and lipid metabolism via peroxisome proliferator-Activated Receptor Alpha

Friend of GATA 2 (FOG2) is a transcriptional co-factor involved mostly in cardiac function. The aim of our current study is to investigate the role of hepatic FOG2 in insulin sensitivity and lipid accumulation. Here, we showed that FOG2 over-expression by adenovirus expressing FOG2 (Ad-FOG2) significantly attenuates insulin signaling in hepatocytes in vitro. Opposite effects were observed when FOG2 was knocked down via adenovirus expressing small-hairpin RNA for FOG2 (Ad-shFOG2). Furthermore, FOG2 knockdown by Ad-shFOG2 ameliorated insulin resistance in leptin receptor-mutated (db/db) mice and FOG2 over-expression by Ad-FOG2 attenuated insulin sensitivity in C57/BL6J wild-type (WT) mice. In addition, Ad-FOG2 reduced whereas Ad-shFOG2 promoted hepatic triglyceride (TG) accumulation in WT mice under fed or fasted conditions, associated with increased or decreased hepatic peroxisome proliferator activated receptor α (ppARα) expression, respectively. Moreover, the improved insulin sensitivity and increased hepatic TG accumulation by Ad-shFOG2 were largely reversed by adenovirus expressing ppARα (Ad-ppARα) in WT mice. Finally, we generated FOG2 liver-specific knockout mice and found that these mice exhibit enhanced insulin sensitivity and elevated hepatic TG accumulation, which were also reversed by Ad-ppARα. Taken together, our results demonstrate a novel function of hepatic FOG2 in insulin sensitivity and lipid metabolism via ppARα.