HNF4α in the Effects of Intermittent Fasting on the Liver
Intermittent fasting strategies such as alternate day fasting are known to be beneficial to health in humans and both health and longevity in animal models. A portion of this outcome likely stems from some degree of reduction in overall calorie intake, but animal studies in which calorie intake is consistent between control and intermittent fasting groups demonstrate that benefits still arise even when calories are not reduced. Lengthy enough periods of hunger likely trigger the same cellular maintenance mechanisms as play a role in the metabolic response to calorie restriction when practiced without fasting. The biochemistry of this response is enormously complex, however. Near everything in cellular metabolism is affected, often in different ways in different organs, and thus even after decades of research, the scientific community is still finding new mechanisms to explore.
In experiments with mice, researchers 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. In particular, the researchers found that the HNF4α protein, which regulates a large number of liver genes, plays a previously unknown role during intermittent fasting.
"For the first time we showed that HNF4α 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." 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 HNF4α means it could be possible to mimic some of the effects of intermittent fasting through the development of liver-specific HNF4α regulators."
Link: https://www.eurekalert.org/pub_releases/2020-03/uos-hif030420.php
My to cents. The mice start dying from starvation after the second day. Non skinny healthy humans can easily go for two weeks without any ill effects, except the discomfort of hunger and having less energy. For us humans probably would take at least 3 days fasting to get to the depletion point mice go in one day. Of course, we might benefit much more since we are longer lived species and should have better repair pathways...
Note of caution to selfexperimenters. Going over too days of fasting requires special break-fast protocol or you risk damage
Hey Cuberat, what kind of break-fast protocol is needed and what is the risk of not following a protocol? Would you have some reference?
@faster
The rule is to start slowly with healthy and easily digestible food. And small portions. Wait for the the first stool before going to solid yeavy food. Breaking the fast requires more discipline and is sometimes harder then the fast itself. Avoid meat and animal products at the beginning. The recommended rule of thumb is for each day of fasting to have half a day transition. There are multiple sources online , albeit with containing advices . Even trying the breaking regimen without fasting is a good calorie restriction ;)
If not following the protocol you risk damaging your stomach and intestines and in some extreme cases , death . This applies to animals too,if your dog or cat haven't eaten for many days you start feeding very small portions.
Smaller risks are that you can get bad habits and start over eating or due to the shock trigger some acute reaction of an otherwise chronic conditions.
The longer the fast the slower you have to go.
Don't go for long fast without trying shorte ones first.
All this being said we have evolved to survive famine and feast at first opportunity, so probably I am too cautious here.