Urea Cycle Defects Linked to Fatty Liver Disease? Study Sheds Light - Video

In a recent study published in Cell Metabolism, revealed a crucial connection between urea cycle defects-which are essential for ammonia detoxification in the body-and the onset of fatty liver disease.

Researchers discovered that defects in the urea cycle cause secondary disruptions in the tricarboxylic acid (TCA) cycle, an essential pathway for energy metabolism. This disruption leads to poor calorie use and excessive fat accumulation in the liver, which can result in inflammation and fibrosis, thereby advancing the progression of the disease.

Fatty liver is considered a major contributor to liver failure and by highlighting the essential role of the urea cycle in the disease's development this research could lead to the creation of new treatments for this currently untreatable condition.

The two main types of fatty liver disease are metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). Both involve excessive fat accumulation in the liver, which can lead to liver failure if not addressed. These conditions are increasingly common among children and often present more severely in this population.

Researchers analyzed blood metabolites from 106,600 healthy participants in the. Her analysis found that certain metabolites linked to nitrogen and energy metabolism, as well as mitochondrial function, could predict the risk of severe liver diseases even in healthy individuals. Cao noted that these findings, supported by both human and mouse research, highlight the crucial role of the urea cycle in understanding severe liver diseases.

Reference: Zhang, Y., et al. (2024). Hierarchical tricarboxylic acid cycle regulation by hepatocyte arginase 2 links the urea cycle to oxidative metabolism. Cell Metabolism. doi.org/10.1016/j.cmet.2024.07.007.