代谢性肝病,肝病 z-bo 2020-10-08 266

　　Diabetes, obesity and non-alcoholic fatty liver disease (NAFLD) are common diseases that can cause serious health consequences. AFLD can develop into inflammatory fibrosis and liver cirrhosis.

　　At present, the molecular causes of NAFLD and NASH are not fully understood. So far, no FDA has approved NAFLD drugs. The main obstacle facing scientists is understanding the causal relationship between NAFLD, diabetes and obesity. These causal relationships usually occur simultaneously in patients and are considered comorbidities. If the cause and root cause are not clear, drug development may fail.

　　The Eugene Applebaum School of Medicine and Health Sciences at Wayne State University is leading a research team to understand the causal relationship between these three diseases and find a cure.

　　Wanqing Liu, associate professor of pharmacy at Wayne State University, and Dr. Eugene Chen, a collaborator at the University of Michigan. Recently, a paper was published in the American Journal of Hepatology through "Mendel Large Genome Analysis Randomness" (this strategy is similar to a randomized clinical trial that relies on the genetic alleles naturally occurring in humans. Randomization.), trying to understand the molecular causes of NAFLD.

　　"We used the genome data of more than 400,000 people from the British Biobank, sequenced the genomes of more than 500,000 residents, and shared health data. In addition, there are nearly 900,000 genomes of people. The data, this is the latest For the first time, the data analysis of the United States was able to determine the causal relationship between NAFLD, type 2 diabetes and obesity."

　　The research team found that NAFLD is mainly "natural" (we found that it can be classified into at least two subtypes (genetically). The subtype caused by "nutrition" and the subtype caused by "nutrition" (mainly due to T2D and other metabolic syndromes or obesity). Genetically driven NAFLD may promote the development of atypical diabetes characterized by hyperglycemia, but it is not always insulin resistant. Surprisingly, NAFLD does not cause Obesity is general, but it does promote the development of central obesity. This subtype of AFLD is also characterized by low cholesterol levels. T2D and obesity or central obesity can lead to the development of NAFLD. In this case, NAFLD can Secondary to T2D or obesity. To further confirm these findings, Liu and his team developed a genetically engineered mouse model that contains three pattatin-like phospholipase domain (PNPLA3) genes, which are human NAFLD Known genetic causes of human mutations. The researchers used the model together with a team in the lab of Dr. Charlie Don from Indiana University School of Medicine to confirm the results of the human genome data.

　　"This research is very important for disease classification, diagnosis, and drug development. It also emphasizes the importance of developing sophisticated medicine in the prevention and treatment of these diseases. For example, research shows that individuals with a high genetic risk of NAFLD seem to" Healthy" because they are thinner, have weak insulin resistance, have low or normal cholesterol levels, but are under NAFLD. Diagnosis may increase the risk of disease progression. Patients with this subtype need to develop drugs for liver genetic causes On the other hand, people with a high genetic risk of diabetes, obesity and NAFLD may benefit from weight loss and blood sugar control."