Researchers at the University of Sydney have identified cellular changes that take place in the liver during intermittent fasting. Led by Dr. Mark Larance, those who conducted the study published in the journal Cell Reports believe that every-other-day fasting can reprogram liver proteins in a way that has extensive metabolic impact.
 
“We know that fasting can be an effective intervention to treat disease and improve liver health. But we haven’t known how fasting reprograms liver proteins, which perform a diverse array of essential metabolic functions,” said Dr Larance, a Cancer Institute of NSW Future Research Fellow in the Charles Perkins Centre and School of Life and Environmental Sciences at the University of Sydney. “By studying the impact on proteins in the livers of mice, which are suitable human biological models, we now have a much better understanding of how this happens.”
 
Mice who were made to fast every other day had significant changes on their liver proteins, showing unexpected impact on fatty acid metabolism, as well as an unexpected role played by a master regulator protein that controls many biological pathways in the liver and other organs.
 
That regulator protein, HNF4-(alpha), is inhibited during intermittent fasting, Larance said. “This has downstream consequences, such as lowering the abundance of blood proteins in inflammation or affecting bile synthesis. This helps explain some of the previously known facts about intermittent fasting.”
 
Every-other-day fasting, where no food is consumed on alternate days, changed the metabolism of fatty acids in the liver. This finding could be applied to improvements in glucose tolerance and diabetes regulation.
 
The study used a technique known as multi-Omics, which considers multiple data sets such as the total collection of proteins and genes. It allowed for the integration of large amounts of information to discover new associations within biological systems.
 
Larance said that the new information yielded from mice can be used to determine optimum fasting periods to regulate protein response in the liver for humans.
 
“Last year we published research into the impact of every-other-day-fasting on humans,” Larance said. “Using the mouse data, we can now build up improved models of fasting for better human health.” 

Additionally, Larance said there is potential for the development of an HNF4-(alpha) inhibitor, which could eventually have many health applications for a number of conditions.