The global rise in obesity and diabetes is causing an epidemic of fatty liver disease, which affects 20-30% of the world’s population. Almost one-third of people with fatty liver disease develop an advanced form of the disease known as non-alcoholic steatohepatitis (NASH), which can progress to cirrhosis and end-stage liver disease, or even liver cancer, and is a major risk factor for cardiovascular disease.
It’s unclear why some people with fatty liver disease remain relatively healthy while others develop potentially life-threatening illnesses. Up until now.
A study published in The Journal of Clinical Investigation led by Professor Tony Tiganis from Monash University’s Biomedicine Discovery Institute has shown that the levels of the NOX4 protein change as the disease progresses — rising in the early stages of the disease to protect the liver, but declining as the liver disease gets worse.
Compounds that bolster the activity of NOX4, or the adaptive program that NOX4 instigates, may be highly beneficial, countering not only the development of NASH, but also improving skeletal and cardiac function, as well as metabolic health.
Professor Tiganis
The researchers discovered that removing NOX4 caused NASH and liver damage in obese mice. Furthermore, when NOX4 levels in these mice were artificially increased, they were protected from NASH and liver damage.
Importantly, the discovery provides evidence for a therapeutic approach to a disease whose prevalence is expected to increase by 63% between 2015 and 2030. According to Professor Tiganis, the precise mechanisms governing the progression to NASH and liver damage are unknown.
“It has been perplexing why the majority of patients with fatty liver disease don’t progress to more severe disease,” he went on to say.
The researchers have shown that this is because NOX4 is induced when the liver first starts to accumulate fat and activates a complex adaptive program that protects the liver. It is only when NOX4 levels decline and this adaptive program is abrogated that obese patients with fatty liver progress to NASH and liver damage.
Importantly, previous research by Professor Tiganis and colleagues has shown that increasing NOX4 levels in skeletal muscle or the heart after exercise protects against damage, promotes muscle and cardiac function, and prevents the metabolic decline associated with aging.
“Compounds that bolster the activity of NOX4, or the adaptive program that NOX4 instigates, may be highly beneficial, countering not only the development of NASH, but also improving skeletal and cardiac function, as well as metabolic health,” said the professor.
These compounds are naturally found in cruciferous vegetables like broccoli and cauliflower.
