Lower calorie intake, while still obtaining required levels of micronutrients, has long been demonstrated to improve near all measures of health, leads to better quality of life, and modestly slows aging. A higher calorie intake leads to visceral fat deposition, metabolic syndrome, type 2 diabetes, fatty liver disease, and a shorter, less healthy life. Separately, fasting appears to have similar influences on health and aging to those produced by a lower calorie intake, but to some degree independently of overall calorie level - though it is worth noting that the body of research here is much smaller than that for calorie restriction without fasting. Since just about every aspect of metabolism is altered by calorie intake, both in the short term and over the long term, researchers attempting to understand how it all works at the detail level have an enormous task ahead of them. They are breaking off pieces of the puzzle one protein at a time, as in the research noted here, and will be doing so for a long time yet:
The growing number of overweight people has long been one of modern society's pressing issues. In particular the resulting metabolic diseases such as type 2 diabetes and corresponding secondary conditions can have serious consequences for health. A reduced intake of calories, such as in the framework of an intermittent fasting diet, can help to whip the metabolism back into shape - but why does this happen? Once we understand how fasting influences our metabolism we can attempt to bring about this effect therapeutically."
In the current study, the scientists looked for liver cell genetic activity differences that were caused by fasting. With the help of transcript arrays, they were able to show that especially the gene for the protein GADD45β was often read differently depending on the diet: the greater the hunger, the more frequently the cells produced the molecule, whose name stands for 'Growth Arrest and DNA Damage-inducible'. As the name says, the molecule was previously associated with the repair of damage to the genetic information and the cell cycle, rather than with metabolic biology. Subsequent simulation tests showed that GADD45β is responsible for controlling the absorption of fatty acids in the liver. Mice who lacked the corresponding gene were more likely to develop fatty liver disease. However when the protein was restored, the fat content of the liver normalized and also sugar metabolism improved.
The scientists were able to confirm the result also in humans: a low GADD45β level was accompanied by increased fat accumulation in the liver and an elevated blood sugar level. "The stress on the liver cells caused by fasting consequently appears to stimulate GADD45β production, which then adjusts the metabolism to the low food intake." The researchers now want to use the new findings for therapeutic intervention in the fat and sugar metabolism so that the positive effects of food deprivation might be translated for treatment.