Mayo Clinic researchers have identified how excessive alcohol use can drive the development of fatty liver disease.
The culprit is a disruption of a protein-recycling enzyme (VCP), which normally prevents fat buildup in liver cells.
The findings may help predict who is most at risk from alcohol-related liver damage and guide new treatments.
Recent surveys have shown a decline in alcohol consumption, particularly among younger consumers. A new study suggests that to be a very healthy trend.
A team of Mayo Clinic researchers has discovered a new biological mechanism that helps explain why excessive alcohol consumption can worsen or contribute to fatty liver disease — a condition affecting more than one-third of U.S. adults and a leading cause of liver failure and cancer.
Also known as Metabolic Dysfunction–Associated Steatotic Liver Disease (MASLD), fatty liver occurs when too much fat builds up in liver cells, or hepatocytes. These cells are responsible for filtering blood, processing nutrients, and breaking down damaged proteins.
Under normal conditions, fat from food is stored in small structures called lipid droplets inside hepatocytes, which the body later taps for energy. But when fat accumulates excessively, it can trigger inflammation, scarring, type 2 diabetes, and even cancer.
Alcohol’s impact on a key enzyme
The Mayo Clinic team zeroed in on a cellular enzyme called valosin-containing protein (VCP). VCP is essential for protein quality control: it works with a partner protein to move damaged proteins into structures called lysosomes, where they are broken down and recycled.
"We were surprised to see VCP removing a specific protein from the surface of the lipid droplet," said Mark McNiven, Ph.D., the study’s senior author. "When that particular protein called HSD17β13 accumulates, the fat content in liver cells balloons and contributes to fatty liver disease."
The study revealed that heavy alcohol consumption disrupts this process. Alcohol exposure nearly eliminates VCP from the lipid droplet surface, preventing it from removing HSD17β13. Without this protective mechanism, HSD17β13 builds up, increasing fat accumulation in the liver.