Study Finds Possible Mechanism
for Link Between Sleep Disturbances and Metabolic
Syndrome
A new mouse study suggests that a brain system that
controls the sleep/wake cycle might also play a role
in regulating appetite and metabolism. Mice with a
mutation in a gene called “Clock,” which
helps drive circadian rhythm, ate significantly more
and gained more weight. The finding could help explain
why disrupted sleep patterns—particularly when
combined with a high-fat diet--are associated with
excessive weight gain and the onset of metabolic syndrome
in some people, according to investigators supported
by the National Institutes of Health (NIH).
The study, by Fred W. Turek, Ph.D., and Joseph Bass,
M.D., Ph.D., of Northwestern University in Evanston,
Ill., and others will be available at the Science
Express website, http://www.sciencemag.org/sciencexpress/recent.shtml,
on April 21, 2005. The National Institute on Aging
(NIA), the National Heart, Lung and Blood Institute
(NHLBI), and the National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK) supported this
work. The NIA, NHLBI and NIDDK are components of the
NIH at the U.S. Department of Health and Human Services.
At least 40 million Americans have chronic sleep problems,
and an additional 20 million experience occasional
sleeping problems. As many as 47 million Americans
have metabolic syndrome, a cluster of conditions shown
to increase a person’s risk of heart disease
and stroke. The National Cholesterol Education Program
defines metabolic syndrome as having at least 3 of
the following risk factors: high blood pressure, high
glucose (sugar) levels which can indicate risk for
diabetes, high triglyceride levels, low levels of
good cholesterol, and a large waist.
Scientists have found that circadian rhythms (which
control the sleep/wake cycle and other biological
processes), hunger, and satiety are all regulated
by centers within a brain structure called the hypothalamus.
And previous studies in humans have suggested that
disrupted sleep patterns may contribute to the development
of obesity, diabetes, and metabolic syndrome.
In this latest work, Turek and his colleagues found
that mutant mice were more active during times when
rodents usually sleep. They also had less fluctuation
in blood levels of leptin, a hormone that transmits
a satiety signal to the brain. The researchers also
found that Clock mutant mice had reduced levels of
the hormone ghrelin within the hypothalamus, indicting
that ghrelin may participate in the neuronal relay
linking sleep, wakefulness, and appetite. Together,
these alterations in neural and peripheral hormones
suggest that a number of previously undetected brain
circuits may exist that are common to sleep and eating.
The mice with a mutation in the Clock gene fed a regular
diet gained about as much weight as normal mice that
were fed a high-fat diet. The mice with a mutation
in the Clock gene showed even greater weight gain
and changes in metabolism when fed a high-fat diet.
They developed a wide range of conditions associated
with obesity, diabetes, and the metabolic syndrome,
such as high levels of blood cholesterol, triglycerides,
and glucose, and insulin resistance.
Andrew Monjan, Ph.D., of the NIA and Carl E. Hunt,
M.D., director of the NIH National Center on Sleep
Disorders Research, are available to discuss this
study. To arrange an interview with Dr. Monjan, phone
(301) 496-1752; for Dr. Hunt, phone (301) 496-4236.
NIA, NHLBI, and NIDDK are part of the National
Institutes of Health (NIH), the Federal Government’s
primary agency for biomedical and behavioral research.
NIH is a component of the U.S. Department of Health
and Human Services. NIA information on conditions
and diseases associated with aging is available at
www.nia.nih.gov. NHLBI press releases and fact sheets,
including information on obesity and sleep disorders
can be found online at www.nhlbi.nih.gov. NIDDK information
on weight control and nutrition can be found online
at www.niddk.nih.gov.
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