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
Intermittent fasting could improve obese women's health
January 8, 2019
Science Daily/University of Adelaide
Research shows that obese women lost more weight and improved their health by fasting intermittently while following a strictly controlled diet.
The study, published in the journal Obesity, involved a sample of 88 women following carefully controlled diets over 10 weeks.
"Continuously restricting their diet is the main way that obese women try to tackle their weight," says Dr Amy Hutchison, lead author from the University of Adelaide and the South Australian Health and Medical Research Institute (SAHMRI).
"Unfortunately, studies have shown that long-term adherence to a restricted diet is very challenging for people to follow, so this study looked at the impact of intermittent fasting on weight loss.
"Obese women who followed a diet in which they ate 70% of their required energy intake and fasted intermittently lost the most weight.
"Other women in the study who either fasted intermittently without reducing their food intake, who reduced their food intake but did not fast, or did not restrict their diet at all, were not as successful in losing weight," says Dr Hutchison.
The study also checked the effect of the different diets on the women's health. Women who fasted intermittently as well as restricting their food improved their health more than those who only restricted their diet or only fasted intermittently.
"By adhering to a strict pattern of intermittent fasting and dieting, obese women have achieved significant weight loss and improvements in their health such as decreased markers for heart disease," says Dr Hutchison.
Participants who fasted intermittently ate breakfast and then refrained from eating for 24 hours followed by 24 hours of eating. The following day they fasted again.
All participants of the study were women who were overweight or obese with a Body Mass Index (BMI) in the 25-40 range and aged between 35 and 70 years. They followed a typical Australian diet consisting of 35% fat, 15% protein and 50% carbohydrate.
"The most successful participants lost approximately 0.5 to 1 kg per week for each week of the study," says Dr Hutchison.
"This study is adding to evidence that intermittent fasting, at least in the short term, may provide better outcomes than daily continuous diet restriction for health and potentially for weight loss," says Associate Professor Leonie Heilbronn from the University of Adelaide and SAHMRI.
"While the study confirms that intermittent fasting is more effective than continuous diet restriction, the underlying signal for limiting people's appetite, which could hold the key to triggering effective weight loss, requires further research."
New trials now being undertaken will examine the effectiveness of long-term fasting on both men and women.
https://www.sciencedaily.com/releases/2019/01/190108125526.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