Understanding Fatty Liver Disease and Potential Treatments

Fatty liver disease is a common condition that affects liver function, with excessive alcohol consumption being a contributing factor to its progression. A recent study has shed light on the biological mechanisms that lead to fat accumulation in liver cells, paving the way for new treatments aimed at preventing or treating this disease.

How the Liver Works

The liver is the body’s primary organ that acts as a filter for everything we consume. Liver cells, or hepatocytes, support this organ by secreting dozens of different proteins while collecting, sorting, breaking down, and recycling everything that passes through it. Fats from the intestines, for example, are absorbed and stored in hepatocytes as fat droplets, which serve as energy sources, especially during fasting periods. However, excessive accumulation of these droplets leads to fatty liver disease.

The Role of the VCP Enzyme

Researchers have found that an enzyme known as the valosin-containing protein (VCP) plays a crucial role in various biological processes, including the recycling of unwanted proteins. The study showed that VCP removes a specific protein from the surface of the fat droplet. When this protein, known as HSD17β13, accumulates, the amount of fat in liver cells increases, leading to fatty liver disease.

In individuals without fatty liver disease, the VCP enzyme appears to maintain a balance of the HSD17β13 protein to prevent excessive fat accumulation in liver cells.

The Impact of Alcohol on Liver Function

The study revealed that excessive alcohol exposure leads to the near-complete removal of the VCP enzyme from the surface of the fat droplet, allowing for significant accumulation of the HSD17β13 protein. This discovery explains how excessive alcohol consumption can exacerbate fatty liver disease.

Researchers also observed the complex recycling mechanism of the VCP enzyme, where it works with a companion protein to transport damaged proteins to a vesicle called the lysosome, which breaks down unwanted proteins.

New Horizons for Treatment

The study’s findings suggest that the HSD17β13 protein is a potential target for new treatments aimed at preventing or treating fatty liver disease. This discovery enhances our understanding of how fat droplets function in the liver and how hepatocytes work to reduce their fat content.

This study may also help predict which patients could be susceptible to the negative effects of alcohol on the liver if this cellular system is disrupted.

Conclusion

This study is part of a larger initiative at the Mayo Clinic aimed at developing tools that enable doctors to predict and intercept biological processes before they develop into diseases or progress to complex and difficult-to-treat conditions. The study provides a deeper understanding of the biological processes leading to fatty liver disease and opens the door for the development of new therapeutic strategies.