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Restricted feeding leads to metabolic benefits in mice

Scientists found that feeding mice twice a day, with complete food restriction in between, improved metabolism and prevented age- and obesity-associated metabolic defects compared to allowing them 24-hour access to food.  Previous research demonstrated that fasting can lead to improved metabolic health and extended life.  Fasting has been shown to activate a cellular process called “autophagy” that removes damaged parts of cells, and this process decreases with obesity and/or aging.  If autophagy is responsible for the metabolic improvements associated with caloric restriction the scientists hypothesized that a feeding strategy that induced robust autophagy—without needing to restrict calories or alter the type of food consumed—might lead to metabolic benefits.

To test this hypothesis, the researchers developed a twice-a-day (TAD) feeding model where mice were fed only during two intervals—one early and one late in a 24-hour period.  TAD mice were compared to a group that had 24-hour access to food, but were otherwise identical.  Importantly, both groups ate the same amount of food.  The scientists found no difference in body weight between the two groups of mice fed a healthful diet after 1 year, but observed that the TAD mice had less body fat and an increase in muscle mass.  Additionally, TAD mice fed a diet that typically causes weight gain and metabolic problems were protected from these.  TAD mice also showed lower blood glucose (sugar) and lipid (fat) levels and an increase in energy expenditure.  By comparing young TAD mice to old TAD mice, the scientists observed that the TAD feeding prevented metabolic defects associated with aging.  Studying the impact of the TAD feeding in multiple tissues—liver, fat, muscle, and brain—the scientists found that the diverse metabolic benefits of TAD feeding were linked to changes in daily cycles of autophagy.  The results raise the possibility that twice-a-day feeding could have similar benefits in humans, although it remains to be tested; and many other factors, such as genetic makeup, may influence the benefits in people.


Martinez-Lopez N, Tarabra E, Toledo M, …Singh R. System-wide benefits of intermeal fasting by autophagy. Cell Metab 26: 856-871.e5,. doi: 10.1016/j.cmet.2017.09.020, 2017.
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