China News Service, May 30. According to Hong Kong Sing Tao.com, a research team led by Hong Kong Baptist University (hereinafter referred to as HKBU) discovered that a protein called "membrane type 1 matrix metalloproteinase" (MT1-MMP) Hydrolase, which plays an important role in the regulation of satiety, provides a potential target for the development of innovative drugs for the treatment of obesity.
The research results have been published in the internationally renowned scientific journal Nature Metabolism.
The most effective way to deal with obesity is to eat less, but obese people often have difficulty adjusting their eating habits because they lose the feeling of fullness.
The research team, led by Assistant Professor Wang Kailiang of the Teaching and Research Department of HKBU School of Chinese Medicine, and Bian Zhaoxiang, Director of the Clinical Department and Professor of Clinical Research of Tsang Shiu-Tian Chinese Medicine, has identified a hydrolytic protease called MT1-MMP, which stimulates satiety in the human brain. It plays a regulatory role in the mechanism of sensory signals.
Growth and differentiation factor 15 is a hormone that signals satiety by binding to neuronal receptors located in the hindbrain called GDNF family receptor alpha-like (GFRAL).
Modulation of GFRAL can affect the ability of GDF15 to signal satiety, thereby helping to regulate food intake.
The team conducted a series of experiments to investigate the regulation of GFRAL by MT1-MMP.
The team conducted mouse model experiments, feeding a high-fat diet to a group of transgenic mice lacking MT1-MMP in satiety neurons, and another group of normal mice that belonged to a control group.
After 16 weeks, mice lacking MT1-MMP ate 10 percent less, gained 50 percent less body weight, and had lower glucose and plasma insulin levels than controls.
The results showed that lack of MT1-MMP prevented the mice from developing obesity caused by a high-fat diet.
Using a technique known as "western blot analysis", which is widely used to detect specific proteins, the team found that the activity of MT1-MMP in the "region rema" and "nucleus solitarius" of obese mice, the brain involved in appetite and weight management. area has increased.
This showed increased MT1-MMP activity in the brains of obese mice, which may be a risk factor for persistent weight gain.
To understand the mechanism by which MT1-MMP inhibits the satiety signal of GDF15, the research team conducted a series of molecular biology experiments using animal models and cultured cells.
The results showed that cells with active MT1-MMP had significantly reduced signaling from GFRAL and even GDF15.
This is because MT1-MMP snips GFRAL from the surface of brain neurons, preventing GDF15 from binding to GFRAL, thereby reducing the amount of satiety signaling, which in turn shields neurons from satiety signaling transmitted by GDF15 .
The researchers also inhibited the activity of MT1-MMP in vivo by pharmacological methods to explore the potential of targeting MT1-MMP to treat obesity.
Metabolic parameters, including food intake, glucose tolerance, and body weight, were significantly improved in obese mice after administration of specific neutralizing antibodies that inhibited MT1-MMP.
The results show that MT1-MMP can be used as a potential therapeutic target for the development of innovative drugs for the treatment of obesity.
Wang Kailiang pointed out that the research results established the role of MT1-MMP in regulating satiety, and initially showed that this proteolytic enzyme is an effective target for the treatment of obesity.
Drug inhibition of MT1-MMP is a feasible strategy to develop drugs that can effectively treat obesity.