Cause of the Non-alcoholic Fatty Liver Disease Identified

Non-alcoholic fatty liver disease is a perplexing syndrome that causes fat to accumulate in the liver for no apparent reason. Researchers at the University of Virginia School of Medicine have identified a critical trigger for this ailment. The new understandings provide an explanation for the problem in young individuals and may assist develop the initial therapy for the most widespread liver disease in the world.

The offender? The cellular compartment that houses our DNA is beginning to wrinkle. These wrinkled cellular nuclei may have a role in common metabolic illnesses including diabetes and fatty liver disease as well as aging itself, according to an earlier study by UVA scientists. The current findings support previous conclusions and may prompt medicines that target wrinkles to prevent fatty liver disease—and perhaps even halt or reverse aging.

“We found a common mechanism involving the nucleus and the nuclear lamina that leads to fat accumulation in the liver in aged individuals and younger people with non-alcoholic fatty liver disease,” said senior researcher Irina M. Bochkis, Ph.D., of UVA’s Department of Pharmacology. Our findings could lead to novel treatments aimed at restoring the function of the nuclear lamina to control aberrant genes and reverse fatty liver in young patients with non-alcoholic fatty liver disease or aged individuals.

Understanding Non-alcoholic Fatty Liver

People who drink a lot frequently develop fatty liver disease, and the presence of excess liver fat is a warning sign of heavy drinking. However, the non-alcoholic fatty liver disease affects those who drink infrequently or never, particularly the elderly and those who have type 2 diabetes. Over the 70s who have the illness make up about 40% of the population.

Many people with fatty liver disease experience no symptoms at all. They might not even be conscious of having it. However, for certain people, it might lead to weakness, exhaustion, and abdominal pain, which can lower the quality of life. There is no cure, which is unfortunate.

The origin of non-alcoholic fatty liver disease has baffled medical professionals, but UVA’s recent research raises the possibility that errors in the “hard drives” that house the instructions on how to operate our cells may be at least partially to blame. These modifications begin in the cell nucleus, where our chromosomes are kept, and change the way some genes function, finally causing fat to build up in the liver.

According to recent findings, the lamina, a region of the nucleus, is where the defect first appears. The nuclear membrane and the chromatin, or genetic material, that resides inside, are connected by the lamina. Bochkis and her team discovered that the activity of genes that regulate the storage of fats is impacted by the development of wrinkles in the lamina. The liver fills up with extra fat when these genes are overactive, which causes non-alcoholic fatty liver disease.

The researchers examined liver cells taken from younger human patients with non-alcoholic fatty liver disease, aged 21–51, to confirm their findings. Wrinkly lamina was exactly what the researchers anticipated to find. The researchers claim that this helps to explain why the illness can affect people of any age and should be helpful for identifying those at risk.

Researchers may be able to create methods to cure or perhaps prevent non-alcoholic fatty liver disease by focusing on the damaging changes in the lamina (and possibly other metabolic diseases and even aging). For instance, according to Bochkis, researchers may be able to utilize specially crafted viruses to send various lamin proteins to the liver in order to smooth the membranes’ surfaces and restore the cells’ normal functionality.

“Currently there is no treatment for non-alcoholic fatty liver disease and no method to stratify the patients,” Bochkis said. “Our findings could lead to improved stratification and a novel treatment without side effects where restoring the lamina function returns the cell to a healthy state with appropriate gene expression.”

The study is published in the journal Genome Research.

Source Link