By :- Team VOH
16 Jun 2024
Fatty liver disease, also known as steatotic liver disease (SLD), is becoming increasingly common and poses a serious health risk. Researchers have now identified a key mechanism that could lead to new treatments. A team from Heinrich Heine University Dusseldorf (HHU)’s Institute of Metabolic Physiology, working with the German Diabetes Centre (DDZ) and other partners, discovered that a saturated fatty acid in blood vessels triggers the production of the signalling molecule SEMA3A, which closes the 'windows' in blood vessels.
These tiny windows, located in the endothelial cells of blood vessels, allow substances to pass between liver cells and the bloodstream. When SEMA3A is produced, these windows close, making it harder for fat to move from the liver to adipose tissue. However, the researchers found that suppressing SEMA3A reopens the windows, reducing the amount of fat in the liver. Their findings were published in the journal Nature Cardiovascular Research.
The study highlights the impact of ‘metabolic dysfunction-associated SLD’ (MASLD), which can develop due to poor lifestyle choices such as a high-energy diet and lack of exercise. MASLD affects about a third of the global population and, while initially asymptomatic, can progress to liver inflammation, cirrhosis, liver failure, or liver cancer. Currently, there is no long-term substitute for liver function akin to dialysis for kidney failure, leaving liver transplants as the only cure for advanced cases.
Additionally, MASLD increases the risk of type 2 diabetes and cardiovascular diseases. Although obesity is a major risk factor, not all obese individuals develop MASLD, and conversely, slim individuals can also be affected. The molecular causes of MASLD are not fully understood, but the HHU and DDZ research team has uncovered an important aspect of its development.
Using scanning electron microscopy, the researchers observed that the windows in the smallest blood vessels of the liver were closed in mice with fatty liver and type 2 diabetes. Sydney Balkenhol, the study's first author, noted this significant finding. Dr. Daniel Eberhard, co-first author, added that inhibiting the SEMA3A molecule could reverse the effect, defatting the liver and improving its function.
Dr. Eckhard Lammert, corresponding author and head of the Institute of Metabolic Physiology at HHU and the Institute of Vascular and Islet Cell Biology at the DDZ, expressed optimism about the potential therapeutic implications for humans. "We hope that our discoveries will lead to a new therapeutic approach for preventing MASLD and its consequences at an early stage. However, detailed investigation in humans is needed first," he stated.
25 Jun 2024
25 Jun 2024
25 Jun 2024
25 Jun 2024
25 Jun 2024