Scientists at the Duke-NUS Medical School in Singapore have discovered the mechanism that leads to an advanced form of fatty liver disease – and vitamin B12 and folic acid supplements can reverse this process.
The findings could help people with nonalcoholic fatty liver disease, a term for a range of liver diseases affecting people who drink little or no alcohol, affecting 25% of all adults worldwide and four in 10 adults in Singapore.
Non-alcoholic fatty liver disease involves the accumulation of fat in the liver and is the leading cause of liver transplantation worldwide. Its high prevalence is due to its association with diabetes and obesity – two major public health problems in Singapore and other industrialized countries. When the condition progresses to inflammation and scar tissue formation, it is called nonalcoholic steatohepatitis (NASH).
“Although the accumulation of fat in the liver is reversible in its early stages, its progression to NASH causes liver dysfunction, cirrhosis, and increases the risk of liver cancer,” said Dr. Madhulika Tripathi, first author of the study, is a senior research fellow in the Laboratory of Hormone Regulation in the Cardiovascular and Metabolic Program at Duke-NUS.
There is currently no pharmacological treatment for NASH because scientists do not understand the mechanics of the disease. Although scientists know that NASH is linked to elevated blood levels of an amino acid called homocysteine, they don’t know what role it plays in the development of the disease.
Dr. Dr. Tripathi, one of the authors of the study. Brijesh Singh and colleagues in Singapore, India, China, and the United States confirmed the association of homocysteine with NASH progression in preclinical models and humans. They also found that as homocysteine levels rise in the liver, amino acids attach to various liver proteins, changing their structure and interfering with their function. Specifically, when homocysteine attached to a protein called syntaxin 17, it blocked the protein’s role in transporting and digesting fats from fatty acids (an important cellular process called autophagy, where cells remove damaged proteins or damaged organelles). metabolism, mitochondrial metabolism and prevention of inflammation. This has fueled the development and progression of NASH fatty liver disease.
Importantly, the researchers found that supplementing the diet with vitamin B12 and folic acid in preclinical models increased the levels of syntaxin 17 in the liver and restored its role in autophagy. It also slowed the progression of NASH and reversed liver inflammation and fibrosis.
“Our findings are interesting and important because they suggest that a relatively inexpensive therapy, vitamin B12 and folic acid, can be used to prevent and/or delay the development of NASH,” said Dr. Singh. “Furthermore, serum and liver homocysteine levels may serve as biomarkers for NASH severity.”
Homocysteine may also affect other liver proteins, and these are future research areas for the team. They hope further research will lead to the development of anti-NASH therapies.
Professor Paul M. Yen, chief of the Laboratory of Hormonal Regulation in the Cardiovascular and Metabolic Disorders Program at Duke-NUS and senior author of the study, said: “The potential for vitamin B12 and folate, which has a high safety profile, as defined by the US Food and Drug Administration as dietary supplements. , first-line therapies for the prevention and treatment of NASH could lead to large cost savings and a reduction in the health burden of NASH in both developed and developing countries.
Professor Patrick Casey, senior associate dean for research at Duke-NUS, said: “Transplantation is currently the only treatment for patients with end-stage liver disease. Dr. Tripathi and his colleagues’ findings show that an accessible and affordable intervention offers new hope for those suffering from fatty liver disease. , can halt or reverse liver damage. The team’s findings underscore the value of basic science research, through which the scientific community is making a huge positive impact on patients’ lives.”
Published in the Journal of Research Journal of Hepatology.
High rates of liver disease and mortality observed in patients with NAFLD/NASH
Madhulika Tripathi et al. Journal of Hepatology (2022). DOI: 10.1016/j.jhep.2022.06.033
Presented by Duke-NUS Medical School
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