Research on mice shows unexpected effect of intermittent fasting on fat metabolism

Australian scientists have implemented sophisticated analytical tools in order to understand the effect of intermittent fasting on the liver, helping to mitigate disease.

Research on mice shows unexpected effect of intermittent fasting on fat metabolism
Dr Mark Larance from the Charles Perkins Centre and School of Life and Environmental Sciences at the University of Sydney. Image Credit: Stefanie Zingsheim/University of Sydney.

The study outcomes will be useful for medical researchers working in the area of diabetes, cancer, and cardiovascular research, helping design new interventions to reduce disease risk and find out the ideal fasting intervals.

Led by Dr Mark Larance from the University of Sydney, researchers performed experiments with mice, determining the effect of every-other-day fasting on proteins in the liver.

The results revealed an unpredicted impact on fatty acid metabolism and the unexpected role of a master regulator protein that regulates several biological pathways in the liver and other organs.

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. 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.”

Dr Mark Larance, Cancer Institute of NSW Future Research Fellow, Charles Perkins Centre and School of Life and Environmental Sciences, University of Sydney

Specifically, it was found that the HNF4-(alpha) protein, which controls various liver genes, plays a hitherto unpredicted 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 added.

Besides, it was found that every-other-day-fasting—where food is not consumed on alternate days—modified the metabolism of fatty acids in the liver.

This insight could be applied to improve glucose tolerance and the control 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 Mark Larance, Cancer Institute of NSW Future Research Fellow, Charles Perkins Centre and School of Life and Environmental Sciences, University of Sydney

The study, which was conducted jointly with the Heart Research Institute and Dr John O’Sullivan at Royal Prince Alfred Hospital, was published in Cell Reports.

Dr O’Sullivan is an Adjunct Professor in the Faculty of Medicine & Health and a Senior Lecturer at the Sydney Medical School.

The researchers used a technique called multi-Omics, which involves considering multiple data sets such as the complete collection of genes and proteins, in the study. This enabled the integration of large amounts of information to discover new links 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.”

Dr O’Sullivan, Adjunct Professor, Faculty of Medicine & Health, University of Sydney

The multi-Omics data was acquired from Sydney Mass Spectrometry, part of the University of Sydney’s Core Research Facilities.

According to Dr Larance, it would now be possible to use the information in future studies to identify the ideal fasting periods to control protein response in the liver.

Last year we published research into the impact of every-other-day-fasting on humans. Using these mouse data, we can now build up improved models of fasting for better human health,” Dr Larance added.

Source:
Journal reference:

Hatchwell, L., et al. (2020) Multi-omics Analysis of the Intermittent Fasting Response in Mice Identifies an Unexpected Role for HNF4α. Cell Reports. doi.org/10.1016/j.celrep.2020.02.051.

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