FGF (fibroblast growth factor) is a peptide protein found in a variety of tissues of the body, which can not only accelerate the regeneration of human tissues, but also regulate human metabolism. The new function of FGF in regulating glycolipid metabolism is an important discovery in recent years, but little is known about how FGF plays a role in glycolipid metabolism and other scientific issues.
In response to this major scientific problem, a team led by Li Xiaokun, academician of the Chinese Academy of Engineering and president of Wenzhou Medical University, conducted in-depth research and discovered for the first time the molecular mechanism of FGF affecting glucose and lipid metabolism. On June 24, the project achievement "New Functions and Mechanisms of Growth Factor FGFs in Regulating Glucose and Lipid Metabolism" won the second prize of the National Natural Science Award.
In the early research, Li Xiaokun's team observed through mouse experiments that when FGF21, a member of the FGF family, was missing, the experimental mice would show metabolic abnormalities, and symptoms such as obesity and fatty liver appeared. However, when the FGF21 drug was given to diabetic mice, the relevant disease indicators could achieve stability and improvement. "Through further research, it has been found that growth factors are related to adiponectin, which is responsible for the operation of lipid metabolism, and can regulate fat, and now there are about 1 billion overweight people in the world, which is tantamount to discovering a big gold mine." Li Xiaokun introduced that in layman's terms, FGF is like a "key", but this "key" is only a prototype and cannot be used directly, but with the help of fat, a membrane protein (Klotho) in the liver, combined with "assembly" as a whole, in order to finally become a usable "key".
"This 'key' can open the 'door' of adiponectin, promote the production of adiponectin, and let it travel to all cells of the body, so as to finally systematically regulate glucose and lipid metabolism and improve diabetes, fatty liver and other diseases." Li Xiaokun said.
In the latest development, the team also found that the diabetes model can maintain a stable state of blood glucose for more than 4 months with FGF drugs, which can be administered once in the central or nasal cavity. In mid-2023, the study will be published in the international academic journal Cell Metabolism. It is reported that the long-term effect of the drug can greatly improve the quality of life of patients.
It is understood that a variety of FGF21 long-acting allosterants have entered the clinical research stage. Among them, two national first-class new drugs for non-alcoholic steatohepatitis and hypertriglycerides have entered phase 2 clinical trials, and have been approved by the US FDA to carry out global clinical trials at the same time.
"In the eyes of others, there is no need to 'drill the horns' in such a small field as growth factors, but for me, it is a 'gold mine', and we just want to make it a global leader." Li Xiaokun's team led the world to overcome the problem of growth factor drugs, and successfully developed three national first-class new drugs for the treatment of refractory ulcers such as war wounds, burns and diabetic feet, benefiting more than 80 million patients clinically, providing a "Chinese solution" for international trauma treatment. Focusing on the key technology and clinical transformation of growth factor drugs, it won the second prize of the 2009 National Technological Invention Award and the second prize of the 2018 National Science and Technology Progress Award.
This project has opened up a new field of regulation of FGF and glycolipid metabolism, consolidated Continental's leading position in the field of global growth factor FGF new drug research and development, and also provided a development paradigm worthy of reference for the research and development of original biological drugs in Continental. "Our ultimate goal is to study the important functions and mechanisms of growth factors, and develop new cell growth factor drugs suitable for Chinese genes to benefit disease patients." Li Xiaokun said.
Carrying out research guided by national strategic needs is the anchoring goal of Academician Li Xiaokun's team. While deeply cultivating basic research, the team actively promotes the construction of the industrialization base of China's gene medicine valley, and has established two high-level platforms, the National Engineering Research Center and the National Key Laboratory, to systematically provide support for the upstream R&D and midstream and downstream industrialization of cell growth factor drugs, and strive to open up the whole process of production, education, research and medicine.
Correspondent: Gao Tuo, Reporter: Xu Huimin