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Scientists discover the role of FOG2 in insulin sensitivity and hepatic lipid metabolism

In recent years, there has been an increase in the global prevalence of type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD). Insulin resistance is the risk factor for T2D and dysregulated hepatic lipid metabolism is the major cause to NAFLD. Exploring the underlying mechanism may provide effective treatment to T2D and NAFLD.

Friend of GATA 2 (FOG2, also known as ZFPM2) is first cloned from mouse embryonic brain and heart and is expressed in many tissues and functions as a co-regulator of transcriptional factor GATA family. Studies have shown that FOG2 is involved in the regulation of many physiological processes, including coronary vascular development and heart morphology. It is unknown, however, whether FOG2 is involved in the regulation of insulin sensitivity and fatty liver.

To answer this question, Dr. Guo and her colleagues, from Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences,  found a novel function of hepatic FOG2 in insulin sensitivity and lipid metabolism. In this study, they found: 1) Knocking down of FOG2 by Ad-shFOG2 improves insulin sensitivity in leptin receptor-deficient mice (db/db), a classic animal model for insulin resistance, while overexpress FOG2 impairs insulin sensitivity in C57/B6J wild-type (WT) nice. 2) Knockdown FOG2 increases hepatic lipid accumulation and overexpress FOG2 decreases lipid accumulation in WT mice. 3) FOG2 exerts its function on insulin sensitivity and lipid metabolism through PPARα activation. 4)The regulation of PPARα by FOG2 is mediated by NR2F2. These findings provide novel insights into the mechanisms underlying insulin sensitivity and lipid metabolism.

This work entitled “A novel function of hepatic FOG2 in insulin sensitivity and lipid metabolism via PPARα” has been published online in the Diabetes on May, 2016.

This work was conducted under the help of Professor Liu Yong from Institute for Nutritional Sciences. This study was supported by research grants from National Natural Science Foundation, the Ministry of Science and Technology of China, and Chinese Academy of Sciences.

Author Contact:
Guo Feifan, Principle Investigator
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Tel: 86-21-54920250
Fax: 86-21-54920291
Email: ffguo@sibs.ac.cn


Mechanisms of hepatic FOG2 in regulating insulin sensitivity and lipid metabolism
Image by Dr.Guo’s lab

Related website: http://diabetes.diabetesjournals.org/search?fulltext=FOG2&submit=yes&x=18&y=9

 
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