How intermittent fasting changes liver enzymes and helps prevent disease
Research on mice reveals surprising impact on fat metabolism
March 10, 2020
Science Daily/University of Sydney
Researchers in Australia have used state-of-the-art analytical tools to understand how intermittent fasting works on the liver to help prevent disease. The findings will help medical scientists working in cancer, cardiovascular and diabetes research develop new interventions to lower disease risk and discover the optimum intervals for fasting.
In experiments with mice, researchers led by Dr Mark Larance at the University of Sydney identified how every-other-day fasting affected proteins in the liver, showing unexpected impact on fatty acid metabolism and the surprising role played by a master regulator protein that controls many 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," 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."
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 said.
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 research, published today in Cell Reports, was done in collaboration with the Heart Research Institute and Dr John O'Sullivan at Royal Prince Alfred Hospital. Dr O'Sullivan is an Adjunct Professor in the Faculty of Medicine & Health and a Senior Lecturer at the Sydney Medical School.
A technique known as multi-Omics, which considers multiple data sets such as the total collection of proteins and genes, was used in the study, allowing for 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 together all the moving parts."
The multi-Omics data was obtained at Sydney Mass Spectrometry, part of the University of Sydney's Core Research Facilities.
Dr Larance said that the information can now be used in future studies to determine optimum fasting periods to regulate 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."
https://www.sciencedaily.com/releases/2020/03/200310164737.htm
Longer daily fasting times improve health and longevity in mice
Benefits seen regardless of calorie intake, diet composition in new study
September 6, 2018
Science Daily/NIH/National Institute on Aging
Increasing time between meals made male mice healthier overall and live longer compared to mice who ate more frequently, according to a new study published in the Sept. 6, 2018 issue of Cell Metabolism. Scientists from the National Institute on Aging (NIA) at the National Institutes of Health, the University of Wisconsin-Madison, and the Pennington Biomedical Research Center, Baton Rouge, Louisiana, reported that health and longevity improved with increased fasting time, regardless of what the mice ate or how many calories they consumed.
"This study showed that mice who ate one meal per day, and thus had the longest fasting period, seemed to have a longer lifespan and better outcomes for common age-related liver disease and metabolic disorders," said NIA Director Richard J. Hodes, M.D. "These intriguing results in an animal model show that the interplay of total caloric intake and the length of feeding and fasting periods deserves a closer look."
The scientists randomly divided 292 male mice into two diet groups. One group received a naturally sourced diet that was lower in purified sugars and fat, and higher in protein and fiber than the other diet. The mice in each diet group were then divided into three sub-groups based on how often they had access to food. The first group of mice had access to food around the clock. A second group of mice was fed 30 percent less calories per day than the first group. The third group was meal fed, getting a single meal that added up to the exact number of calories as the round-the-clock group. Both the meal-fed and calorie-restricted mice learned to eat quickly when food was available, resulting in longer daily fasting periods for both groups.
The scientists tracked the mice's metabolic health through their lifespans until their natural deaths and examined them post-mortem. Meal-fed and calorie-restricted mice showed improvements in overall health, as evidenced by delays in common age-related damage to the liver and other organs, and extended longevity. The calorie-restricted mice also showed significant improvement in fasting glucose and insulin levels compared to the other groups. Interestingly, the researchers found that diet composition had no significant impact on lifespan in the meal fed and calorie restricted groups.
According to the study's lead author, Rafael de Cabo, Ph.D., chief of the Translational Gerontology Branch of the NIA Intramural Research Program, scientists have studied the beneficial effects of caloric restriction for more than a century, but the impact of increased fasting times has recently come under closer scrutiny.
"Increasing daily fasting times, without a reduction of calories and regardless of the type of diet consumed, resulted in overall improvements in health and survival in male mice," said de Cabo. "Perhaps this extended daily fasting period enables repair and maintenance mechanisms that would be absent in a continuous exposure to food."
The researchers say their findings are encouraging for future studies on how these types of time-restricted eating patterns might help humans to maintain healthy weight and reduce some common age-related metabolic disorders. According to de Cabo, next steps for this research include expanding these findings to other strains of mice and other lab animal species using both sexes, and to find the potential translation of the findings in humans.
For more information on what the research shows about calorie restriction and fasting diets in humans visit: https://www.nia.nih.gov/health/calorie-restriction-and-fasting-diets-what-do-we-know
https://www.sciencedaily.com/releases/2018/09/180906123305.htm
Changes in breakfast and dinner timings can reduce body fat
August 30, 2018
Science Daily/University of Surrey
Modest changes to breakfast and dinner times can reduce body fat, a new pilot study reports.
During a 10-week study on 'time-restricted feeding' (a form of intermittent fasting), researchers led by Dr Jonathan Johnston from the University of Surrey investigated the impact changing meal times has on dietary intake, body composition and blood risk markers for diabetes and heart disease.
Participants were split into two groups -- those who were required to delay their breakfast by 90 minutes and have their dinner 90 minutes earlier, and those who ate meals as they would normally (the controls). Participants were required to provide blood samples and complete diet diaries before and during the 10-week intervention and complete a feedback questionnaire immediately after the study.
Unlike previous studies in this area, participants were not asked to stick to a strict diet and could eat freely, provided it was within a certain eating window. This helped researchers assess whether this type of diet was easy to follow in everyday life.
Researchers found that those who changed their mealtimes lost on average more than twice as much body fat as those in the control group, who ate their meals as normal. If these pilot data can be repeated in larger studies, there is potential for time-restricted feeding to have broad health benefits.
Although there were no restrictions on what participants could eat, researchers found that those who changed their mealtimes ate less food overall than the control group. This result was supported by questionnaire responses which found that 57 percent of participants noted a reduction in food intake either due to reduced appetite, decreased eating opportunities or a cutback in snacking (particularly in the evenings). It is currently uncertain whether the longer fasting period undertaken by this group was also a contributing factor to this reduction in body fat.
As part of the study, researchers also examined if fasting diets are compatible with everyday life and long term commitment. When questioned, 57 percent of participants felt they could not have maintained the new meal times beyond the prescribed 10 weeks because of their incompatibility with family and social life. However, 43 per cent of participants would consider continuing if eating times were more flexible.
Dr Jonathan Johnston, Reader in Chronobiology and Integrative Physiology at the University of Surrey, said:
"Although this study is small, it has provided us with invaluable insight into how slight alterations to our meal times can have benefits to our bodies. Reduction in body fat lessens our chances of developing obesity and related diseases, so is vital in improving our overall health.
"However, as we have seen with these participants, fasting diets are difficult to follow and may not always be compatible with family and social life. We therefore need to make sure they are flexible and conducive to real life, as the potential benefits of such diets are clear to see.
"We are now going to use these preliminary findings to design larger, more comprehensive studies of time-restricted feeding."
https://www.sciencedaily.com/releases/2018/08/180830084826.htm