Fatty liver disease, also known as steatotic liver disease (SLD), is increasingly causing liver failure. Researchers from Heinrich Heine University Düsseldorf and partners found that a saturated fatty acid triggers SEMA3A.
This molecule closes ‘windows’ in blood vessels, blocking fat transport from the liver to adipose tissue. In Nature Cardiovascular Research, they discovered that inhibiting SEMA3A reopens these windows, reducing fat accumulation in the liver.
Metabolic dysfunction-associated steatotic liver disease (MASLD) can develop due to poor lifestyle habits like high-calorie diets and lack of exercise. It affects about a third of people globally, starting without symptoms but can progress to liver inflammation.
In the long term, it may lead to severe conditions like cirrhosis, liver failure, or cancer. Unlike kidney failure, where dialysis can help, there’s no long-term substitute for liver function except transplantation. MASLD also increases the risk of type 2 diabetes and cardiovascular diseases. While obesity increases MASLD risk, not all higher weight individuals get it, and some slim people can develop the disease, too.
Researchers from HHU, DDZ, Düsseldorf University Hospital, and FZJ found a key reason behind MASLD. They discovered that tiny openings (fenestrae) in liver blood vessel cells, crucial for moving fats out, are closed by a molecule called SEMA3A. This happens when blood vessels are exposed to too much palmitic acid, a saturated fatty acid.
Sydney Balkenhol from HHU and DDZ, lead author of the study in Nature Cardiovascular Research, highlighted their findings using electron microscopy. In mice with fatty liver and type 2 diabetes, the tiny blood vessel “windows” were closed.
Dr. Daniel Eberhard, another lead author, added, “We could reverse this effect. By blocking the signaling molecule, we reduced fat in the liver and improved its function.”
The study concludes that inhibiting the signaling molecule SEMA3A can reopen the tiny “windows” in liver blood vessels, allowing excess fat to be transported out of the liver. This new approach reduces liver fat and improves liver function, offering a potential treatment for fatty liver disease.
Journal reference:
- Eberhard, D., Balkenhol, S., Köster, A. et al. Semaphorin-3A regulates liver sinusoidal endothelial cell porosity and promotes hepatic steatosis. Nature Cardiovascular Research. DOI: 10.1038/s44161-024-00487-z.