Scientists from Glasgow Caledonian University have identified a key biological pathway that could prevent fatty liver disease—triggered by high-fat, high-sugar diets—from progressing to deadly liver cancer.
The team, working with the Cancer Research UK (CRUK) Scotland Institute in Glasgow and The Francis Crick Institute in London, has published their potentially life-saving research ‘p53 and TIGAR promote redox control to protect against metabolic dysfunction-associated steatohepatitis’ in JHep Reports, a leading journal in the field of Gastroenterology and Hepatology.
Liver cancer is a widespread and lethal condition, particularly prevalent in Scotland. Cases arising from underlying fatty liver disease, caused by the overconsumption of a fat and sugar rich diet, are on the rise. Currently no effective therapies exist to stop the progression of fatty liver disease to liver cancer as there is still a lack of understanding of the mechanisms involved.
Cancer experts in the School of Health and Life Sciences’ Department of Biological and Biomedical Sciences, the CRUK Scotland Institute, and The Francis Crick Institute, previously identified the tumour suppressor gene p53 as crucial in protecting the liver against toxins.
Now they have built on that work by discovering that p53 also protects the liver from the damaging effects of a high-fat, high-sugar diet. The team delved even deeper to find out how p53 actually carries out its protective effects. Scientists found this is through a target gene downstream of p53, known as TIGAR, which acts as an antioxidant and detoxifies lipids in a fatty liver.
This latest breakthrough suggests antioxidant therapy could be developed to mimic the protective response of p53 and TIGAR. This would prevent the development of some of the key features of fatty liver disease.
Dr Timothy Humpton, who leads the ‘Liver p53 lab’ at Glasgow Caledonian, worked on the research paper with his PhD student Celine Wittke, who is co-first author with Dr Eric Cheung, from The Francis Crick Institute.
Dr Humpton said: “This research has established a key role for p53 and TIGAR in protecting against the progression from liver disease to liver cancer. Targeting this through the use of antioxidants is of great interest for future therapies aiming to prevent liver cancer.”
“Many people still don’t realise that a bad diet full of fat and sugar, and the lack of exercise, can actually cause fatty liver disease which can progress to liver cancer, so it’s not just people who drink alcohol that are susceptible.
“Fatty liver disease is hard to diagnose because it’s asymptomatic for the most part. That’s why liver cancer prognosis is so poor in these patients. It’s frequently not flagged until it’s advanced cancer.”
“We are hoping that an antioxidant therapy can be developed through the results of our p53 and TIGAR research to help reverse some of the damage done to the liver by the Western diet high in fat and sugar.”
Reader Dr Humpton is part of the School of Health and Life Sciences’ Research Centre for Health (ReaCH) Molecular Mechanisms of Long-term Conditions Research Group.