B vitamins can potentially be used to treat a

How B vitamins could potentially treat or prevent non-alcoholic steatohepatitis in people with non-alcoholic fatty liver disease

image: Western-style diets, which are typically high in fructose intake, can lead to elevated levels of serum and liver homocysteine ​​in the blood (a medical condition known as hyperhomocysteinemia), which the research team found is directly proportional to the severity of non-alcoholic steatohepatitis (NASH) in people with non-alcoholic fatty liver disease that has progressed to NASH. They showed that hyperhomocysteinemia causes homocysteinylation of the key autophagy protein STX17, leading to inhibition of autophagy during NASH development and progression. Vitamin B12 and folate supplementation not only restored autophagy (an essential cellular process by which cells remove misshapen proteins or damaged organelles), but also reduced the overall pathology of NASH.
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Credit: Duke-NUS School of Medicine

SINGAPORE, August 5, 2022 – Scientists at the Duke-NUS School of Medicine in Singapore have discovered a mechanism that leads to an advanced form of fatty liver disease, and it turns out that vitamin B12 and folic acid supplementation could reverse this process.

These findings could help people with nonalcoholic fatty liver disease, an umbrella term for a variety of liver conditions that affect people who drink little or no alcohol, which affects 25 percent of all adults worldwide. world and four out of 10 adults in Singapore.

Non-alcoholic fatty liver disease involves the accumulation of fat in the liver and is one of the leading causes of liver transplants 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 known as non-alcoholic steatohepatitis (NASH).

“While liver fat deposition is reversible in its early stages, its progression to NASH causes liver dysfunction, cirrhosis, and increases the risk of liver cancer,” said study first author Dr. Madhulika Tripathi, principal investigator from the Hormone Regulation Laboratory at Duke-NUS’ Cardiovascular and Metabolic Program.

Currently, there are no drug treatments for NASH because scientists do not understand the mechanics of the disease. Although scientists know that NASH is associated with elevated blood levels of an amino acid called homocysteine, they didn’t know what role, if any, it plays in the development of the disorder.

Dr. Tripathi, study co-author Dr Brijesh Singh and colleagues in Singapore, India, China, and the US confirmed the association of homocysteine ​​with NASH progression in preclinical and human models. They also found that as liver homocysteine ​​levels increased, the amino acid bound to various liver proteins, changing their structure and preventing their function. In particular, when homocysteine ​​bound to a protein called syntaxin 17, it prevented the protein from carrying out its function of transporting and digesting fat (known as autophagy, an essential cellular process by which cells remove misshapen proteins or damaged organelles ) in fatty acid metabolism. mitochondrial turnover and prevention of inflammation. This induced the development and progression of fatty liver disease to NASH.

Importantly, the researchers found that supplementing the diet in the preclinical models with vitamin B12 and folic acid increased levels of syntaxin 17 in the liver and restored its function in autophagy. It also slowed the progression of NASH and reversed liver inflammation and fibrosis.

“Our findings are exciting and important because they suggest that a relatively inexpensive therapy, vitamin B12 and folic acid, could be used to prevent and/or slow the progression of NASH,” said Dr. Singh. “In addition, serum and liver homocysteine ​​levels could serve as biomarkers of NASH severity.”

Homocysteine ​​may similarly affect other liver proteins, and finding out what they are is a future research direction for the team. They hope that further research will lead to the development of NASH therapies.

Professor Paul M. YenChief of the Hormone Regulation Laboratory in the Duke-NUS Cardiovascular and Metabolic Disorders Program, and lead author of the study, said: The US Food and Drug Administration, as first-line therapies for prevention and treatment of NASH could result in huge cost savings and reduce the health burden of NASH in both developed and developing countries.”

professor patrick casey, senior vice dean for research at Duke-NUS, said, “Currently, the only treatment for patients with end-stage liver disease is to receive a transplant. The findings of Dr. Tripathi and her colleagues demonstrate that a simple, affordable and accessible intervention could potentially stop or reverse liver damage, bringing new hope to those with fatty liver disease. The team’s findings underscore the value of basic scientific research, through which the scientific community continues to have a major positive impact on the lives of patients.”

The research was published in the Journal of Hepatology.

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