Fat accumulation in the liver due to defects in lipoprotein assembly or transport can lead to fatty liver disease or hepatic steatosis. Fatty liver disease is one of the most prevalent forms of chronic liver disease worldwide. The very low density lipoprotein (VLDL) is a major type of lipoprotein. VLDL assembly and secretion from the liver plays an important role in controlling plasma levels of triacylglycerols (TGs) and cholesterol. However, the underlying molecular mechanism for VLDL transport is still poorly understood.
Scientists from XU Zhiheng’s group at the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, found that high fat diet induced overexpression of meningioma-expressed antigen 6 (Mea6) in mice liver, indicating Mea6 protein might be related to lipid metabolism.
In order to examine the physiological function of Mea6, they knocked out Mea6 gene in mouse liver by using genome-editing strategy. Their data indicated that hepatocyte-specific deletion of Mea6 led to severe fatty liver and hypolipemia in mice. Further analyses indicate that Mea6 deletion impairs the secretion of different types of lipids and proteins, including VLDL, from the liver.
Moreover, they demonstrate that Mea6 interacts with subunits of the endoplasmic reticulum (ER) coat protein complex II (COPII) to cause lipid accumulation in hepatocytes. Taking together, Mea6 plays a critical role in lipid transportation through the coordinated regulation of the COPII machinery.
Their findings provide insight into mechanisms underlying VLDL transportation. More importantly, this mouse model provides a useful tool for potential biomarkers or drug screening related to fatty liver disease.
This study entitled “Mea6 controls VLDL transport through the coordinated regulation of COPII assembly” was published online in Cell Research. This work is supported by grants from National Natural Science Foundation of China and the Ministry of Science and Technology of China.
Model of Lipid transport through cooperation of Mea6 with COPII subunits (Image by IGDB)
Contact:
Dr. XU Zhiheng
Email: zhxu@genetics.ac.cn
