Clock ticking with new plan to fight Alzheimer's

"background-image:url('http://l1.yimg.com/bt/api/res/1.2/X1I7hg5TtpXMkD7Tvh5vug--/YXBwaWQ9eW5ld3M7Zmk9ZmlsbDtoPTExMztweW9mZj0wO3E9ODU7dz0xNTA-/http://l.yimg.com/dh/ap/ap/default/120515/weight.jpg');" width

View the Original article

Less sleep, disrupted internal 24-hour clock means higher risk of diabetes and obesity

ScienceDaily (Apr. 11, 2012) — A study by researchers at Brigham and Women's Hospital (BWH) reinforces the finding that too little sleep or sleep patterns that are inconsistent with our body's "internal biological clock" may lead to increased risk of diabetes and obesity. This finding has been seen in short-term lab studies and when observing human subjects via epidemiological studies. However, unlike epidemiological studies, this new study provides support by examining humans in a controlled lab environment over a prolonged period, and altering the timing of sleep, mimicking shift work or recurrent jet lag.

See Also:Health & MedicineSleep Disorder ResearchInsomnia ResearchDiabetesMind & BrainSleep DisordersInsomniaObstructive Sleep ApneaReferenceCircadian rhythm sleep disorderJet lagCircadian rhythmSleep deprivation

The study will be electronically published on April 11, 2012 in Science Translational Medicine.

Researchers hosted 21 healthy participants in a completely controlled environment for nearly six weeks. The researchers controlled how many hours of sleep participants got, as well as when they slept, and other factors such as activities and diet. Participants started with getting optimal sleep (approximately 10 hours per night). This was followed by three weeks of 5.6 hours of sleep per 24-hour period and with sleep occurring at all times of day and night, thereby simulating the schedule of rotating shift workers. Thus, during this period, there were many days when participants were trying to sleep at unusual times within their internal circadian cycle-the body's "internal biological clock" that regulates sleep-wake and many other processes within our bodies. The study closed with the participants having nine nights of recovery sleep at the usual time.

The researchers saw that prolonged sleep restriction with simultaneous circadian disruption decreased the participants' resting metabolic rate. Moreover, during this period, glucose concentrations in the blood increased after meals, because of poor insulin secretion by the pancreas.

According to the researchers, a decreased resting metabolic rate could translate into a yearly weight gain of over 10 pounds if diet and activity are unchanged. Increased glucose concentration and poor insulin secretion could lead to an increased risk for diabetes.

"We think these results support the findings from studies showing that, in people with a pre-diabetic condition, shift workers who stay awake at night are much more likely to progress to full-on diabetes than day workers," said Orfeu M. Buxton, PhD, BWH neuroscientist and lead study author. "Since night workers often have a hard time sleeping during the day, they can face both circadian disruption working at night and insufficient sleep during the day. The evidence is clear that getting enough sleep is important for health, and that sleep should be at night for best effect."

This research was supported by the National Institute on Aging; National Heart, Lung and Blood Institute; National Center for Research Resources; Center for Clinical Investigation of the Harvard Clinical and Translational Science Center; Joslin Diabetes and Endocrinology Research Center Service Specialized Assay Core; the National Space Biomedical Research Institute; and Natural Sciences and Engineering Research Council of Canada.

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

View the Original article

Compounds dramatically alter biological clock and lead to weight loss, animal study suggests

ScienceDaily (Mar. 29, 2012) — Scientists from the Florida campus of The Scripps Research Institute have synthesized a pair of small molecules that dramatically alter the core biological clock in animal models, highlighting the compounds' potential effectiveness in treating a remarkable range of disorders -- including obesity, diabetes, high cholesterol, and serious sleep disorders.

See Also:Health & MedicineDiet and Weight LossObesityMind & BrainDieting and Weight ControlInsomniaPlants & AnimalsMiceAgriculture and FoodReferenceCircadian rhythmCircadian rhythm sleep disorderJet lagDiabetes mellitus type 2

The study was published on March 29, 2012, in an advance, online edition of the journal Nature.

The study showed that when administered in animal models the synthetic small molecules altered circadian rhythm and the pattern of core clock gene expression in the brain's hypothalamus, the site of the master cellular clock that synchronizes daily rhythms in mammals; circadian rhythms are the physiological processes that respond to a 24-hour cycle of light and dark and are present in most living things.

When given to diet-induced obese mice, these same small molecules decreased obesity by reducing fat mass and markedly improving cholesterol levels and hyperglycemia -- chronically high blood sugar levels that frequently lead to diabetes.

"The idea behind this research is that our circadian rhythms are coupled with metabolic processes and that you can modulate them pharmacologically," said Thomas Burris, a professor at Scripps Florida who led the study. "As it turns out, the effect of that modulation is surprisingly positive -- everything has been beneficial so far."

Burris stressed that these compounds were first generation -- the first to hit their targets in vivo with room for improvement as potential treatments. "In terms of therapeutics, this is really the first step," he said.

In the new study, the team identified and tested a pair of potent synthetic compounds that activate proteins called REV-ERBα and REV-ERBβ, which play an integral role in regulating the expression of core clock proteins that drive biological rhythms in activity and metabolism.

In the study, the scientists observed clear metabolic effects when the synthetic compounds were administered twice a day for 12 days. Animals displayed weight loss due to decreased fat mass with no changes in the amount of food they ate. The animals followed the human model of obesity closely, eating a standard Western diet of high fat, high sugar foods, yet still lost weight when given the compounds.

In one of the study's more striking findings, both synthetic compounds were shown to reduce cholesterol production. Cholesterol in the blood of treated animal models decreased 47 percent; triglycerides in the blood decreased 12 percent.

The circadian pattern of expression of a number of metabolic genes in the liver, skeletal muscle, and in fat tissue was also altered, resulting in increased energy expenditure, something of a surprise. In the study, the scientists observed a five percent increase in oxygen consumption, suggesting increased energy expenditure during the day and at night. However, these increases were not due to increased activity -- the animals displayed an overall 15 percent decrease in movement during those same time periods.

In addition to its impact on metabolism, the two compounds also affected the animals' activity during periods of light and darkness, suggesting that this class of compound may be useful for the treatment of sleep disorders, including the common problem of jet lag.

The first authors of the study, "Regulation of Circadian Behavior and Metabolism by Synthetic REV‐ERB Agonists," are Laura A. Solt and Yongjun Wang of Scripps Research. Other authors include Subhashis Banerjee, Travis Hughes, Douglas J. Kojetin, Thomas Lundasen, Youseung Shin, Jin Liu, Michael D. Cameron, Romain Noel, Andrew A. Butler, and Theodore M. Kamenecka of Scripps Research; and Seung‐Hee Yoo and Joseph S. Takahashi of the Howard Hughes Medical Institute and University of Texas Southwestern Medical Center.

The study was supported by the National Institutes of Health and the Howard Hughes Medical Institute.

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

View the Original article