CHARLOTTESVILLE, Va. — Most of science involves small findings that help answer a big question. But once in a while, there is a breakthrough that could change the lives of millions. In this case, researchers from the University of Virginia School of Medicine say they’ve cracked the secret behind what triggers non-alcoholic fatty liver disease. The surprising answer? Wrinkles!
Non-alcoholic fatty liver disease is a condition where fat builds up in the organ, despite patients drinking little or no alcohol. While there are certain risk factors that increase NAFLD risk — obesity, high cholesterol, Type 2 diabetes — there has never been a clear explanation of why the disease manifests in the first place.
In the current study, the researchers found the culprit to be the formation of “wrinkles” in the cellular areas holding our DNA. Previous studies have linked these same wrinkles to other metabolic diseases such as diabetes and accelerated aging. The latest findings could potentially clear the path for treatment and potentially give clues on slowing down or reversing the aging process. It may also explain why some young people develop NAFLD, when a majority of cases typically develop after the age of 70.
“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,” says Irina M. Bochkis, PhD, a senior researcher at the University of Virginia School of Medicine’s department of pharmacology, in a media release. “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.”
Could doctors smooth out liver wrinkles to stop NAFLD?
The team looked at liver cells taken from people between 21 and 51 years-old diagnosed with non-alcoholic fatty liver disease. Results showed the disease seems to come from changes in the nucleus, the center of operations in the cells. In a portion of the nucleus lies the lamina. The lamina acts as a cord tying the nuclear membrane and genetic material known as chromatin. When the lamina forms wrinkles, it affects the activity of genes involved in storing fat. When the genes are overexpressed, the liver is overcapacity with excess fat, leading to non-alcoholic fatty liver disease.
“Currently there is no treatment for non-alcoholic fatty liver disease and no method to stratify the patients,” Bochkis explains. “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.”
One strategy Bochkis and her colleagues are exploring are engineering viruses to deliver different lamin proteins to the liver to smooth out the wrinkles. An unwrinkled surface would, hopefully, return the cell to a healthy state with normal gene activity.
The study is published in the journal Genome Research.
