Circadian Rhythm Key Treating Metabolic Disorders
January 29, 2014

Are Circadian Rhythms The Key To Treating Obesity And Diabetes?

Lee Rannals for - Your Universe Online

New therapies for obesity and diabetes could be developed based on a study that looks at circadian rhythms and the body's internal clock.

The mammalian circadian rhythm is the 24-hour oscillations of biological processes that take place in living organisms. University of California, Santa Barbara (UCSB) researchers studying this clock have found a way to help reset the metabolic clock, which could help people suffering from metabolic disorders like obesity and diabetes.

“Our group has been fascinated with circadian rhythms for over 10 years now, as they represent a marvelous example of robust control at the molecular scale in nature,” Frank Doyle, chair of UCSB’s Department of Chemical Engineering and the principal investigator for the UCSB team, said in a statement. “We are constantly amazed by the mechanisms that nature uses to control these clocks, and we seek to unravel their principles for engineering applications as well as shed light on the underlying cellular mechanisms for medical purposes.”

The team was able to model the mechanisms of two small-molecule drugs that regulate the expression of the clock proteins. The findings shed light on the mechanisms behind the metabolic aspect of circadian rhythm, paving the way for drug therapies that could reduce the risk of disease for those with disrupted rhythms.

Peter St. John, a researcher in the Department of Chemical Engineering and lead author of the study, said blood pressure varies with time of day, along with visual activity, smell and taste. Certain hormones are released at various points during the day so they can do their tasks. Genes and proteins that are expressed in a cell and their activities also change with time of day.

“These oscillations are caused by genetic circuits. So you’ll have a gene that’s produced, and when it’s in its finished form, it will turn itself off,” said St. John.

The healthiest circadian rhythms take place when different and complementary processes occur in the body during distinct and regular daytime and nighttime phases. These healthy rhythms are referred to as 'high amplitude.'

“If you’re fasting at night and you’re asleep, the demands on your cells will be very different than if you’re awake and running around. There’s this temporal separation between the genes that you need during the day and those you need at night,” explained St. John.

Problems start to take place when the amplitude is repressed due to variables like irregular sleep hours, eating too late or exercising too late in the evening. These patterns don’t allow for the necessary nighttime-phase cellular activity, leading to disorders like diabetes, heart disease and obesity.

The team found that if they stabilized the regulation of the clock proteins called Period (PER), you get higher amplitude rhythms, but stabilizing Cryptochrome (CRY) proteins leads to lower-amplitude rhythms.

The researchers are planning future studies to look into whether there is an optimal phase for taking one drug or the other to improve the amplitude or circadian rhythms. Future experiments will look at improving specificity and bioavailability.