How intermittent fasting adjustments liver enzymes and prevents illness

Dr. Mark Larance of the Charles Perkins Center and the School of Life and Environmental Sciences at the University of Sydney. Photo credit: Stefanie Zingsheim / University of Sydney

Studies on mice show surprising effects on lipid metabolism.

Researchers in Australia have used cutting-edge analytical tools to understand how intermittent fasting affects the liver to help prevent disease. The results will help health professionals in cancer, cardiovascular, and diabetes research develop new interventions to reduce the risk of disease and determine the optimal intervals for fasting.

In experiments with mice, researchers led by Dr. Mark Larance of the University of Sydney on how daily fasting affected proteins in the liver and revealed unexpected effects on fat acid Metabolism and the surprising role of a major regulatory protein that controls many biological pathways in the liver and other organs.

“We know fasting can be an effective tool in treating disease and improving liver health. However, we don’t know how fasting reprograms liver proteins that perform a variety of essential metabolic functions, ”said Dr. Larance, an NSW Future Research Fellow cancer institute at the Charles Perkins Center and the School of Life and Environmental Sciences at the University of Sydney.

“By studying the effects on proteins in the livers of mice, which are appropriate human biological models, we now have a much better understanding of how this happens.”

In particular, the researchers found that the HNF4 (alpha) protein, which regulates a large number of liver genes, plays a previously unknown role in intermittent fasting.

“For the first time we have shown that HNF4- (alpha) is inhibited during intermittent fasting. This has downstream consequences, such as B. the reduction in the frequency of blood proteins in inflammation or the influence of bile synthesis. This helps explain some of the previously known facts about intermittent fasting, ”said Dr. Larance.

The researchers also found that alternating day fasts – with no food being eaten on alternate days – changed the metabolism of fatty acids in the liver. This knowledge could be applied to improvements in glucose tolerance and the regulation of diabetes.

“What’s really exciting is that this new understanding of the role of HNF4- (alpha) means that it might be possible to mimic some of the effects of intermittent fasting by developing liver-specific HNF4- (alpha) regulators,” said the author Dr. Larance said.

The study, published today in Cell Reports, was conducted in collaboration with the Heart Research Institute and Dr. John O’Sullivan of the Royal Prince Alfred Hospital. Dr. O’Sullivan is an associate professor in the Faculty of Medicine and Health and a senior lecturer at Sydney Medical School.

The study used a technique known as multi-omics, which takes into account multiple sets of data such as the entire collection of proteins and genes, and allows the integration of large amounts of information to discover new associations within biological systems.

Dr. O’Sullivan said, “These multi-omics approaches give us unprecedented insight into biological systems. We are able to build very sophisticated models by bringing all moving parts together. “

The multi-omics data was obtained from Sydney Mass Spectrometry, part of the Sydney University’s nuclear research facility.

Dr. Larance said the information can now be used in future studies to determine optimal fasting periods for regulating protein response in the liver.

“Last year we published research on the effects of fasting every other day on humans. With this mouse data, we can now build improved models of fasting for better human health. “

Reference: “Multi-Omics Analysis of Intermittent Fasting Response in Mice Identifies an Unexpected Role for HNF4α” by Luke Hatchwell, Dylan J. Harney, Michelle Cielesh, Kieren Young, Yen Chin Koay, John F. O’Sullivan, and Mark Larance, Jan. March 2020, Cell Reports.
DOI: 10.1016 / j.celrep.2020.02.051

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