These 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 (left) had much higher levels of liver fat
(white) than one restricted to an 8-hour daily feeding window (right). Credit:
Courtesy of the Salk Institute for Biological Studies
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 May
17 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."
Hatori cautioned that
people should not jump to the conclusion that eating lots of unhealthy food is
alright as long as we fast. "What we showed is under daily fasting the
body can fight unhealthy food to a significant extent," she says.
"But there are bound to be limits."
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.
The daily feeding-fasting
cycle activates liver enzymes that breakdown cholesterol into bile acids,
spurring the metabolism of brown fat - a type of "good fat" in our
body that converts extra calories to heat. Thus the body literally burns fat
during fasting.
The liver also shuts down
glucose production for several hours, which helps lower blood glucose. The
extra glucose that would have ended up in the blood - high blood sugar is a
hallmark of diabetes - is instead used to build molecules that repair damaged
cells and make new DNA.
This helps prevent
chronic inflammation, which has been implicated in the development of a number
of diseases, including heart disease, cancer, stroke and Alzheimer's. Under the
time-restricted feeding schedule studied by Panda's lab, such low-grade inflammation
was also reduced.
"Implicit in our
findings," says Panda, "is that the control of energy metabolism is a
finely-tuned process that involves an intricate network of signaling and
genetic pathways, including nutrient sensing mechanisms and the circadian
system. Time-restricted feeding acts on these interwoven networks and moves
their state toward that of a normal feeding rhythm."
Amir Zarrinpar, a
co-first author on the paper from the University of California San Diego, said
it was encouraging that a simple increase in daily fasting time prevented
weight gain and the onset of disease.
"Otherwise, this
could have been only partly achieved with a number of different pills and with
adverse side effects," he says.
The multimillion-dollar
question is what these findings mean for humans. Public health surveys on
nutrition have focused on both the quality and quantity of diet, but they have
inherent flaws such as sampling bias, response bias and recall errors that make
the results questionable. Thus, says Panda, with the current data it is
difficult to connect when we eat, what we eat with how much weight we gain.
"The take-home
message," says Panda, "is that eating at regular times during the day
and overnight fasting may prove to be beneficial, but, we will have to wait for
human studies to prove this."
The good news, he adds,
is that most successful human lifestyle interventions were first tested in
mice, so he and his team are hopeful their findings will follow suit. If
following a time-restricted eating schedule can prevent weight gain by 10 to 20
percent, it will be a simple and effective lifestyle intervention to contain
the obesity epidemic.
More information: Hatori et al.: "Time-Restricted Feeding without Reducing
Caloric Intake Prevents Metabolic Diseases in Mice Fed a High-Fat Diet."
Publishing in the Cell Metabolism, June 6, 2012 print issue print
issue.
Journal reference: Cell Metabolism
Provided by Salk
Institute
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