A research team consisting of Kanazawa Institute of Technology, Tokushima University, Kagawa University, and National Institute of Advanced Industrial Science and Technology has found that decreased expression of brain-derived neurotrophic factor BDNF is associated with non-alcoholic steatohepatitis (NASH), a liver disease. The research revealed that it is involved in the development of metabolic dysfunction-associated steatohepatitis (currently called metabolic dysfunction-associated steatohepatitis (MASH)).
BDNF, a neurotrophic factor that functions in the brain, is known as an essential protein for brain functions such as brain development, memory, and learning, but its role is not limited to the brain, but also plays a role in controlling eating and weight. It has been reported thatIn this study, when we examined the peripheral organs of mice with reduced expression of BDNF, we discovered that they exhibited significant fatty liver and also developed NASH.
From this, the research team suspected a link between decreased brain function and the development of NASH, and examined liver tissues and gene expression changes in mice with decreased expression of BDNF.As a result, we found all the clinical characteristics of human NASH, including obesity, hyperglycemia, hyperinsulinemia, fat accumulation, inflammation and fibrosis in the liver, and inflammatory features in adipose tissue as extrahepatic lesions.Furthermore, genetic behavior revealed impaired lipid metabolism, neutrophil infiltration, and increased oxidative stress, and these analyzes also confirmed that mice with reduced BDNF expression developed NASH.
It is known that mice with reduced expression of BDNF cause obesity-related metabolic disorders such as overeating. Therefore, the research team subjected mice with reduced expression of BDNF to restricted feeding, thereby demonstrating the direct effect of BDNF on the liver that is independent of obesity. I also looked into it.As a result, even though weight gain and rise in blood sugar levels were suppressed, infiltration of inflammatory cells including neutrophils occurred in the liver.In other words, this result suggests that decreased expression of BDNF induces liver inflammation through a mechanism independent of obesity, suggesting a direct relationship between BDNF and the development of NASH.
The results of this research are expected to be useful in understanding the onset mechanism of NASH, which is a worldwide problem as a lifestyle-related disease of the liver, and in developing treatments for it.
Paper information:【The Journal of Pathology】Brain-derived neurotrophic factor knock-out mice develop non-alcoholic steatohepatitis
