Fatty liver disease (steatotic liver disease, SLD for short) is a growing cause of liver failure. A team of researchers has found that a saturated fatty acid in the blood vessels triggers the production of the signaling molecule SEMA3A, which closes the ”windows” in the blood vessels. This blocks the transport of fat from the liver to the adipose tissue. The researchers have observed that inhibiting SEMA3A reopens the windows and reduces the fat in the liver.The liver is an important organ in the body. A research team from the Institute of Metabolic Physiology at Heinrich Heine University Düsseldorf (HHU), in partnership with the German Diabetes Centre (DDZ) and other collaborators, has made a discovery. They found that a certain saturated fatty acid in the blood vessels causes the production of a signaling molecule called SEMA3A. This molecule closes the ‘windows’ in the blood vessels, which then hinders the transportation of fat from the liver to the adipose tissue. The researchers published their findings in the journal Nature Cardiovascular Research, reporting that when SEMA3A is inhibited, the windows open again and the fat in the liver is reduced.ular, ‘metabolic dysfunction-associated SLD’ (MASLD for short) can arise as a result of unhealthy lifestyle choices such as a high-calorie diet and lack of physical activity. It currently impacts about one-third of the global population. At the outset, MASLD does not have any harmful effects, but it can progress to liver inflammation. Over time, this could lead to liver cirrhosis, liver failure, or even liver cancer. Unlike kidney failure, there is no alternative treatment that can sustain liver function in the long term, like dialysis for the kidneys. Individuals with MASLD are at a high risk and may require a liver transplant for a potential cure.
Additionally, individuals with MASLD have a increased likelihood of developing other metabolic disorders, including type 2 diabetes and cardiovascular disease. These coexisting conditions can further exacerbate the impact of MASLD on overall health. Therefore, it is imperative to address the root causes of MASLD through lifestyle modifications and proper medical care.Understandably, not all obese individuals are affected, and conversely, slim individuals can also develop the disease. The molecular causes of MASLD are still not fully understood. However, a team of researchers have recently made an important discovery that sheds light on how MASLD develops. They found that the windows (fenestrae) in the endothelial cells of blood vessels play a major role in the development of MASLD.The liver exchanges substances with the blood through tiny windows, allowing it to release excess fat particles into the bloodstream for storage in adipose tissue. Researchers found that a signalling molecule called SEMA3A is responsible for closing these windows when blood vessels are exposed to high levels of the saturated fatty acid “palmitic acid.” Sydney Balkenhol from the Institute of Metabolic Physiology at HHU and the DDZ, who led the study published in Nature Cardiovascular Research, highlighted this discovery.Electron microscopy of liver blood vessels revealed that the “windows” were closed in mice with fatty liver and type 2 diabetes mellitus. Dr. Daniel Eberhard, another primary author, noted that they were able to reverse this effect by inhibiting the signaling molecule, which defatted the liver and improved its function. Corresponding author Dr. Eckhard Lammert, Professor and Head of the Institute of Metabolic Physiology at HHU and the Institute of Vascular and Islet Cell Biology at the DDZ, is hopeful that these findings will eventually lead to a therapeutic approach for humans. He believes that it may be possible to improve liver function in humans using this approach.It may be possible to use the SEMA3A signaling molecule we discovered to stop MASLD and its effects at the beginning. But, we need to carefully study the processes in humans first.
