Multi-Omics Study Reveals How Intermittent Fasting Impacts Liver Proteins

According to researchers in Australia, intermittent fasting changes liver enzymes and helps prevent disease. In a paper published in Cell Reports today, the team identified how every-other-day fasting affected proteins in the liver.

"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 senior author Mark Larance.

In particular, the researchers found that the HNF4-(alpha) protein, which regulates a large number of liver genes, plays a previously unknown role during intermittent fasting. "For the first time we showed that HNF4-(alpha) is inhibited during intermittent fasting. 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," Dr. Larance explained.

The researchers also found that every-other-day-fasting—where no food was consumed on alternate days—changed the metabolism of fatty acids in the liver, knowledge that could be applied to improvements in glucose tolerance and the regulation of diabetes.

"What's really exciting is that this new knowledge about the role of HNF4-(alpha) means it could be possible to mimic some of the effects of intermittent fasting through the development of liver-specific HNF4-(alpha) regulators," Dr. Larance said.

The team relied on multiple data sets such as the total collection of proteins and genes for the study, which allowed for the integration of large amounts of information to discover new associations within biological systems. "These multi-Omics approaches give us unprecedented insight into biological systems. We are able to build very sophisticated models by bringing together all the moving parts, " co-author John O’Sullivan added.