A recent study published on Mar. 9 reports that the tumor suppressor gene EVA1A plays a key role in regulating the fatty acid transporter CD36 in metabolic dysfunction-associated steatotic liver disease (MASLD). The research, led by Associate Professor Ning Li at Qingdao University, highlights a potential new therapeutic target for one of the most common chronic liver diseases worldwide.
MASLD is marked by excessive lipid accumulation in liver cells and is closely linked to rising rates of insulin resistance, obesity, and diabetes. The disease can progress to more severe conditions such as steatohepatitis, hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. Currently, treatment options are limited to lifestyle and dietary changes, with no effective drugs or therapies available.
The study found that CD36 expression and its palmitoylation—a modification affecting how it transports fatty acids—are regulated by EVA1A. In patients with hepatocellular carcinoma and concurrent fatty liver disease, EVA1A levels were significantly reduced. Using genetically engineered mice lacking Eva1a specifically in the liver, researchers observed pronounced hepatic steatosis and disrupted fat metabolism. This suggests that loss of EVA1A directly contributes to lipid imbalance in the liver.
Further experiments involved restoring Eva1a expression in obese ob/ob mice using an adeno-associated virus delivered through tail-vein injection. This intervention improved liver steatosis and suppressed CD36 activity in the liver.
The findings introduce the EVA1A-CD36 axis as a novel mechanism underlying MASLD development and point toward new avenues for therapy targeting this pathway.
