In an experiment the images of liver tissue show the difference in fat accumulation between two groups of mice fed a high-fat diet. A mouse allowed to eat 24 hours a day had much higher levels of liver fat than one restricted to an 8-hour daily feeding window.

It turns out that when we eat may be as important as what we eat. Scientists at the Salk Institute for Biological Studies have found that regular eating times and extending the daily fasting period may override the adverse health effects of a high-fat diet and prevent obesity, diabetes and liver disease in mice.

In a paper published in Cell Metabolism, scientists from Salk’s Regulatory Biology Laboratory reported that mice limited to eating during an 8-hour period are healthier than mice that eat freely throughout the day, regardless of the quality and content of their diet. The study sought to determine whether obesity and metabolic diseases result from a high-fat diet or from disruption of metabolic cycles.

“It’s a dogma that a high-fat diet leads to obesity and that we should eat frequently when we are awake,” says Satchidananda Panda, an associate professor in the Regulatory Biology Laboratory and senior author of the paper. “Our findings, however, suggest that regular eating times and fasting for a significant number of hours a day might be beneficial to our health.”

Panda’s team fed two sets of mice, which shared the same genes, gender and age, a diet comprising 60 percent of its calories from fat (like eating potato chips and ice-cream for all your meals). One group of mice could eat whenever they wanted, consuming half their food at night (mice are primarily nocturnal) and nibbling throughout the rest of the day. The other group was restricted to eating for only eight hours every night; in essence, fasting for about 16 hours a day. Two control groups ate a standard diet comprising about 13 percent of calories from fat under similar conditions.

After 100 days, the mice who ate fatty food frequently throughout the day gained weight and developed high cholesterol, high blood glucose, liver damage and diminished motor control, while the mice in the time-restricted feeding group weighed 28 percent less and showed no adverse health effects despite consuming the same amount of calories from the same fatty food. Further, the time-restricted mice outperformed the ad lib eaters and those on a normal diet when given an exercise test.

“This was a surprising result,” says Megumi Hatori, a postdoctoral researcher in Panda’s laboratory and a first author of the study. “For the last 50 years, we have been told to reduce our calories from fat and to eat smaller meals and snacks throughout the day. We found, however, that fasting time is important. By eating in a time-restricted fashion, you can still resist the damaging effects of a high-fat diet, and we did not find any adverse effects of time-restricted eating when eating healthy food.”

Obesity is a major health challenge in many developed countries, reaching global pandemic proportions. According to the Centers for Disease Control and Prevention, more than one-third of American adults and 17 percent of youth are obese. Obesity increases the risk of a number of health conditions including: high blood pressure, high cholesterol and type 2 diabetes. Lifestyle modifications, including eating a healthy diet and daily exercise, are first-line interventions in the fight against obesity. The Salk study suggests another option for preventing obesity by preserving natural feeding rhythms without altering dietary intake.

Scientists have long assumed that the cause of diet-induced obesity in mice is nutritional; however, the Salk findings suggest that the spreading of caloric intake through the day may contribute, as well, by perturbing metabolic pathways governed by the circadian clock and nutrient sensors.

The Salk study found the body stores fat while eating and starts to burn fat and breakdown cholesterol into beneficial bile acids only after a few hours of fasting. When eating frequently, the body continues to make and store fat, ballooning fat cells and liver cells, which can result in liver damage. Under such conditions the liver also continues to make glucose, which raises blood sugar levels. Time-restricted feeding, on the other hand, reduces production of free fat, glucose and cholesterol and makes better use of them. It cuts down fat storage and turns on fat burning mechanisms when the animals undergo daily fasting, thereby keeping the liver cells healthy and reducing overall body fat.