Fatty liver disease (steatotic liver disease, SLD) is a growing concern, with research showing that it can lead to liver failure. A recent study led by researchers at the Institute of Metabolic Physiology at Heinrich Heine University Düsseldorf (HHU) in collaboration with the German Diabetes Centre (DDZ) has uncovered a key link between a saturated fatty acid in blood vessels and the production of a signalling molecule called SEMA3A. This molecule closes the ‘windows’ in blood vessels, hindering the transport of fat from the liver to adipose tissue. However, when SEMA3A is inhibited, the windows open again, reducing fat accumulation in the liver.
In particular, metabolic dysfunction-associated SLD (MASLD) can arise from poor lifestyle choices such as a high-energy diet and lack of exercise. This condition affects a significant portion of the global population and can lead to liver inflammation and potentially more serious conditions like cirrhosis or liver cancer. While there is no long-term substitute for liver function, such as dialysis for kidney failure, a liver transplant may offer a potential cure for those affected.
Individuals with MASLD also face an increased risk of developing type 2 diabetes and cardiovascular diseases, highlighting the interconnected nature of metabolic disorders. While obesity is a common risk factor for MASLD, the disease can also affect slim individuals, emphasizing the need for a deeper understanding of its molecular origins.
A team of researchers from HHU, DDZ, Düsseldorf University Hospital (UKD), and Forschungszentrum Jülich (FZJ) has made significant strides in uncovering the mechanisms behind MASLD. They found that the closure of windows in endothelial cells, through which fat particles are exchanged between liver cells and the bloodstream, is regulated by the signalling molecule SEMA3A when exposed to saturated fatty acids like palmitic acid.
Through their research, the team observed the closure of these windows in mice with fatty liver and type 2 diabetes, pointing to a potential therapeutic target for addressing MASLD. By inhibiting SEMA3A, they were able to reverse the effects and improve liver function.
Dr. Eckhard Lammert, the corresponding author of the study and head of the Institute of Metabolic Physiology at HHU, is optimistic about the potential implications of their findings for future treatments: “Our discovery of the SEMA3A signalling pathway opens up new possibilities for preventing MASLD and its associated complications. Further research is needed to translate these findings into practical therapies for humans.”
The study, published in Nature Cardiovascular Research, sheds light on the intricate link between fatty liver disease and metabolic dysfunction, providing new insights into potential treatment strategies for this growing health issue.
