The alarming increase in obesity and diabetes worldwide has resulted in a significant rise in the prevalence of fatty liver disease, affecting approximately 20% to 30% of the global population. Within this group, nearly one-third of individuals develop a more advanced form of the disease known as non-alcoholic steatohepatitis (NASH), which can progress to cirrhosis, end-stage liver disease, and even liver cancer. Moreover, NASH is a major risk factor for cardiovascular disease. The reason behind why some individuals with fatty liver disease remain relatively healthy while others face potentially life-threatening complications has remained a mystery. However, a recent study published in The Journal of Clinical Investigation has shed light on this issue.
Led by Professor Tony Tiganis from Monash University’s Biomedicine Discovery Institute, the study reveals that the levels of the NOX4 protein change as the disease progresses. Specifically, NOX4 levels rise in the early stages of fatty liver disease to protect the liver, but decline as the disease worsens. The researchers discovered that removing NOX4 in obese mice led to the development of NASH and liver damage. Conversely, artificially increasing NOX4 levels in these mice provided protection against NASH and liver damage.
This finding is significant as it opens up potential therapeutic possibilities for a disease that is expected to see a 63% increase in prevalence from 2015 to 2030. According to Professor Tiganis, the mechanisms underlying the transition from fatty liver disease to NASH and liver damage have remained elusive. The fact that the majority of patients with fatty liver disease do not progress to severe complications has puzzled researchers for a long time.
The study shows that the reason behind this is the induction of NOX4 when the liver first starts to accumulate fat. NOX4 activates a complex adaptive program that protects the liver. The progression to NASH and liver damage only occurs when NOX4 levels decline and this adaptive program is disrupted in obese patients with fatty liver disease.
Furthermore, previous studies conducted by Professor Tiganis and his colleagues have demonstrated that raising NOX4 levels in skeletal muscle or the heart after exercise not only protects against damage but also promotes muscle and cardiac function. It even prevents the metabolic decline typically associated with aging. Therefore, compounds that enhance the activity of NOX4 or its associated adaptive program may prove highly beneficial. They could not only prevent the development of NASH but also improve skeletal and cardiac function, as well as metabolic health.
Interestingly, such compounds are naturally found in cruciferous vegetables such as broccoli or cauliflower. These vegetables contain specific compounds that can bolster the activity of NOX4 and potentially offer protection against fatty liver disease progression.
In conclusion, this study provides valuable insights into the role of NOX4 protein in fatty liver disease progression. By understanding the mechanisms behind this process, researchers can explore potential therapeutic approaches that target NOX4 or its associated adaptive program. These developments may have far-reaching implications for preventing NASH, improving organ function, and promoting overall metabolic health.
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
