When You Eat May Be Just as Vital to Your Health as What You Eat
pautrey2
ScienceDaily (Nov. 26, 2009) — When you eat may be just as vital to
your health as what you eat, found researchers at the Salk Institute
for Biological Studies. Their experiments in mice revealed that the
daily waxing and waning of thousands of genes in the liver -- the
body's metabolic clearinghouse -- is mostly controlled by food intake
and not by the body's circadian clock as conventional wisdom had it.
"If feeding time determines the activity of a large number of genes
completely independent of the circadian clock, when you eat and fast
each day will have a huge impact on your metabolism," says the study's
leader Satchidananda (Satchin) Panda, Ph.D., an assistant professor in
the Regulatory Biology Laboratory.
The Salk researchers' findings, which will be published in a
forthcoming issue of the Proceedings of the National Academy of
Sciences, could explain why shift workers are unusually prone to
metabolic syndrome, diabetes, high cholesterol levels and obesity.
"We believe that it is not shift work per se that wreaks havoc with
the body's metabolism but changing shifts and weekends, when workers
switch back to a regular day-night cycle," says Panda.
In mammals, the circadian timing system is composed of a central
circadian clock in the brain and subsidiary oscillators in most
peripheral tissues. The master clock in the brain is set by light and
determines the overall diurnal or nocturnal preference of an animal,
including sleep-wake cycles and feeding behavior. The clocks in
peripheral organs are largely insensitive to changes in the light
regime. Instead, their phase and amplitude are affected by many
factors including feeding time.
The clocks themselves keep time through the fall and rise of gene
activity on a roughly 24-hour schedule that anticipates environmental
changes and adapts many of the body's physiological function to the
appropriate time of day.
"The liver oscillator in particular helps the organism to adapt to a
daily pattern of food availability by temporally tuning the activity
of thousands of genes regulating metabolism and physiology," says
Panda. "This regulation is very important, since the absence of a
robust circadian clock predisposes the organism to various metabolic
dysfunctions and diseases."
Despite its importance, it wasn't clear whether the circadian rhythms
in hepatic transcription were solely controlled by the liver clock in
anticipation of food or responded to actual food intake.
To investigate how much influence rhythmic food intake exerts over the
hepatic circadian oscillator, graduate student and first author
Christopher Vollmers put normal and clock-deficient mice on strictly
controlled feeding and fasting schedules while monitoring gene
expression across the whole genome.
He found that putting mice on a strict 8-hour feeding/16-hour fasting
schedule restored the circadian transcription pattern of most
metabolic genes in the liver of mice without a circadian clock.
Conversely, during prolonged fasting, only a small subset of genes
continued to be transcribed in a circadian pattern even with a
functional circadian clock present.
"Food-induced transcription functions like a metabolic sand timer that
runs for 24 hours and is continually reset by the feeding schedule
while the central circadian clock is driven by self-sustaining rhythms
that help us anticipate food, based on our usual eating schedule,"
says Vollmers. "But in the real world we don't eat at the same time
every day and it makes perfect sense to increase the activity of
metabolic genes when you need them the most."
For example, genes that encode enzymes needed to break down sugars
rise immediately after a meal, while the activity of genes encoding
enzymes needed to break down fat is highest when we fast. Consequently
a clearly defined daily feeding schedule puts the enzymes of
metabolism in shift work and optimizes burning of sugar and fat.
"Our study represents a seminal shift in how we think about circadian
cycles," says Panda. "The circadian clock is no longer the sole driver
of rhythms in gene function, instead the phase and amplitude of
rhythmic gene function in the liver is determined by feeding and
fasting periods -- the more defined they are, the more robust the
oscillations become."
While the importance of robust metabolic rhythms for our health has
been demonstrated by shift workers' increased risk of developing
metabolic syndrome, the underlying molecular reasons are still
unclear. Panda speculates that the oscillations serve one big purpose:
to separate incompatible processes, such as the generation of DNA-
damaging reactive oxygen species and DNA replication.
Panda, for one, has stopped eating between 8 pm and 8 am and says he
feels great. "I even lost weight, although I eat whatever I want
during the day," he says.
Researchers who also contributed the work include postdoctoral
researcher Luciano DiTacchio, Ph.D., graduate students Sandhyarani
Pulivarthy and Shubhrox Gill, as well as research assistant Hiep Le,
all in the Regulatory Biology Laboratory.
The work was funded in part by the National Institutes of Health and
the Pew Scholars Program in Biomedical Sciences.
--------------------------------------------------------------------------------
Story Source:
Adapted from materials provided by Salk Institute.