Friday, April 6, 2012

Link between biological clock and metabolic disorders

Our biological clock sets our daily rhythm, and is located somewhere in the brain, above our eyes. The brain centre that controls your circadian rhythm is called the suprachiasmatic nucleus (SCN) and scientists have already largely discovered how it works, and how it affects your body. There is an in-built daily rhythm, which can be externally affected by light. New research shows the internal workings of the SCN and the clock mechanisms in our body may actually be rather different than what is currently known. Additionally, it tells us something about how the biological clock affects the body's metabolism and corresponding disorders. It may lead to new treatment for all kinds of diseases.

Experiments conducted in mice by scientists from Salk Institute for Biological Studies showed that two known components in the SCN play a bigger role than previously thought. Two receptors called REV-ERBα and REV-ERBβ were knocked out in mice, which resulted in problems with maintaining a normal sleeping and eating cycle. Both receptors are active in various parts of the body, presumably to receive the required signals that allow for a 'normal' rhythm.

In their studies, the scientists not only found that the sleep cycle in mice was disrupted when the two receptors are knocked down, but they also saw big differences in metabolism. Both receptor α and β appear to be regulating the expression of many genes including those involved with managing metabolism. The scientists found that mice without the two receptors had high levels of fat and sugar in their blood, which is quite unhealthy and can lead to all sorts of problems such as diabetes and atherosclerosis.

Both receptors share similarities with the way two other components of the circadian rhythm work. Two genes, called Clock and Bmal1, were originally thought to be the core mechanisms of the biological clock. Both genes regulate the activity of hundreds of other genes and thereby basically set the rhythm of many parts of our body. It seems that the activity of REV-ERBα and REV-ERBβ is equally important, integrating the two with the core mechanisms of the clock. Previously, it was thought that the two receptors are merely accessory signals for regulating the circadian rhythm, but it appears they are more important than just backups.
A basic overview on regulation of the clocks. Clock and Bmal1 bind each other and consequently affect the activity of various genes. It results in all kinds of behaviour, as shown in the picture above. 
Because we have seen what effect the two receptors have on regulating metabolism, they may be suitable targets for new therapies. People with sleep disorders could be treated by targeting either receptor α or β. Additionally, it is known that those lacking a proper circadian rhythm are at higher risk of metabolic disorders; they could potentially be treated by targeting the receptors as well. It may decrease the risk of developing all sorts of metabolic or cardiovascular diseases.

The biological clock is an interesting mechanism. It automatically sets our rhythm to a 24 hour schedule, but also regulates other bodily behaviour. Things such as feelings of pain, awareness, body temperature and appetite are examples. It is interesting to see that many forms of behaviour are subjected to a certain rhythm, despite us not really noticing it. Previous research shows that a single gene is responsible for waking you up, and another study showed that a particular group of cells is supposed to keep you awake.

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