Diabetes is emerging as a worldwide epidemic, and China has the largest population of diabetic patients. In China, about one out of ten adults is diagnosed as diabetes; five out of ten as prediabetes. Among diabetes, 80~90% were type II diabetes, characterized as insulin resistance. Besides, a large amount of type II diabetic patients were characterized as obesity, indicating a tight relationship between obesity and type II diabetes.
Mediator is a multi-protein complex composed of about 25 to 30 subunits that functions as a bridge connecting transcription factors and RNA polymerase II transcription machinery for gene transcription.
Previous work from Prof. WANG Gang’s group at Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences(CAS), has demonstrated that Mediator subunit MED23 is a “Yin-Yang” regulator playing opposing roles during the adipogenesis and muscle differentiation, implying the underlying function of Mediator subunit MED23 in energy metabolism(Genes & Dev. 2012; Dev Cell. 2009.).
In the present study, Professor WANG Gang and his team discovered the new role of MED23 in glucose and lipid metabolism, metabolic disorders and type II diabetes.
They first established a liver-specific Med23 knockout mice, and found that deletion of liver Mediator subunit Med23 improved glucose metabolism and prevented diet-induced obesity. Furthermore, glucose tolerance was significantly improved in obese mice after acute deletion of MED23. Finally, they showed that liver MED23 participates in gluconeogenesis through modulating transcription factor FOXO1 activity.
Overall, these findings reveal that Mediator MED23 could become a potential therapeutic target to treat pathologies underlying insulin resistance states, such as diabetes, obesity, and metabolic syndrome, which constitute a huge burden worldwide.
The research entitled “Liver Med23 ablation improves glucose and lipid metabolism through modulating FOXO1 activity” was published online on Cell Research on September 16, 2014. This work was supported by grants from CAS, the Ministry of Science and Technology of China, and the National Natural Science Foundation of China.
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