New research finds activated vitamin D regulates genes involved in the circadian rhythm

Posted on: September 28, 2014   by  Will Hunter

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Research from Journal of Biological Rhythms discovered that calcitriol, the activated form of vitamin D, modulated the expression of and synchronized two genes involved in the circadian rhythm in stem cells derived from fat tissue.

The circadian rhythm is an internal, entrainable biological process that predictably fluctuates over the course of 24 hours. It is involved in the sleeping and feeding patterns of animals, including humans.

Being internal means that it occurs in organisms despite any outside input. Being entrainable means that it can be reset by external influences. The circadian rhythm affects core body temperature, brain wave activity, hormone production, cell regeneration, and other biological activities.

Sunlight is a Zeitgeber which means “time giver” in German. A Zeitgeber is any external or environmental cue that entrains an organism’s biological rhythms to the Earth’s 24 hour light/dark cycle.

It is relatively known that the sun plays a major role in regulating the circadian rhythm in humans. This is one reason why night-shift workers have abnormal sleep schedules; they are not exposing themselves to the sun during the day which alters the reset of the circadian rhythm.

It is unknown, however, how the sun exactly entrains the circadian rhythm.

Therefore researchers from Mexico hypothesized that activated vitamin D may be mediating the effects of sunlight on biological rhythms.

To test this hypothesis, they isolated stem cells from fat tissue and separated them into three different cultures:

  • Serum-shocked culture without calcitriol
  • Serum-shocked culture supplemented with calcitriol
  • Culture supplemented with just calcitriol
  • Culture without serum-shocking or supplemental calcitriol which served as the control

Serum-shocking is the treatment of cell cultures with high levels of serum, which is a supplement added to cell cultures to affect specific changes in the cells. Previous research has shown that serum-shocked cells have induced expression of genes involved with circadian rhythm.

Calcitriol exerts its many effects by binding to the vitamin D receptor, which in turn regulates protein production by increasing or decreasing gene expression. As a result scientists will often administer calcitriol to a single cell type in vitro to see how the genes of these cells respond.

The researchers wanted to see how calcitriol administration affected the expression of two genes involved in the circadian rhythm over a 60 hour period.

They found that serum-shocked cultures without calcitriol administration and with calcitriol administration as well as cultures supplemented with just calcitriol resulted in an increase in the gene expression of the two genes compared to the control group. Not only was there an increase in gene expression in these three groups, but the two genes were synchronized in their expression, meaning their individual expression peaked and waned in a similar rhythm.

The researchers concluded,

“Gene expression profiles of BMAL1 and PER2 over a 60-h period in synchronized [stem cells] using 1α,25-(OH)2D3 suggest an important role of this hormone in the maintenance of circadian rhythms at the cellular level.”

They went on to add,

“Since circadian rhythm influences many physiological processes in all living organisms, this could be the key to better understand the mechanisms by which 1α,25-(OH)2D3 performs many of its assigned functions.”

Because this was an in vitro study, it may not accurately convey what is happening inside a biological organism. Organisms are composed of complex biochemical systems and no biochemical reaction exists in a vacuum. That is, there are many variables at play and an incomprehensible number of interactions take place every moment inside an organism.

Controlled trials in which researchers measure multiple biomarkers influenced by the circadian rhythm (such as testosterone, cortisol, melatonin) are needed to determine how vitamin D supplementation affects this process in humans.

Source

Gutierrez-Monreal M, et al. A Role for 1α,25-Dihydroxyvitamin D3 in the Expression of Circadian Genes. Journal of Biological Rhythms, 2014. 

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