A new study by researchers from the Mayo Clinic researchers has shown how excessive alcohol consumption contributes to fatty liver disease, a condition where too much fat builds up inside the liver cells. Specifically, the research reveals that exposure to excessive alcohol alters an important enzyme called valosin-containing protein (VCP) that recycles damaged proteins.

“We were surprised to see VCP removing a specific protein from the surface of the lipid droplet. When that particular protein called HSD17β13 accumulates, the fat content in liver cells balloons and contributes to fatty liver disease,” said Dr. Mark McNiven, senior author on the study, in a press release.

In individuals without fatty liver disease, the enzyme VCP helps regulate the protein HSD17β13, preventing liver cells from building up too many lipid droplets. However, the researchers observed that heavy alcohol exposure nearly eliminates VCP from the surface of lipid droplets, which in turn allows HSD17β13 to accumulate extensively.

The researchers also observed VCP’s intricate recycling process in action. They saw it work together with a chaperone protein to transport damaged proteins to a lysosome, where the unwanted proteins were broken down. “It was astounding to see this. We tried several experiments to confirm what we were seeing, and every result indicated VCP directs the HSD17β13 protein from the lipid droplet to the lysosome,” said Dr. Sandhya Sen, a Mayo Clinic research fellow and the lead author of the study.

According to Dr. McNiven, these findings mean that HSD17β13 could become a target for potential new therapies to prevent or treat fatty liver disease. “This study increases our understanding of the biology of lipid droplets, the central culprit of fatty liver, and how the hepatocyte works in an effort to reduce its fat content,” Dr. McNiven said. “It also could help predict which patients are prone to the detrimental effect of excessive alcohol consumption on their liver if this cellular system is compromised.”