'Internal Body Clock' Gene Drug May Combat Obesity And Diabetes

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Drugs that affect the brain's "biological clock" may help combat obesity, high cholesterol and diabetes, early research suggests.

Two synthetic molecules were used to alter the activity of "clock" genes that control night-and-day based body functions.

Most living things, including humans, possess circadian rhythms that respond to 24-hour cycles of light and dark.

When the new compounds were given to obese mice, they reduced their fat and cholesterol levels. The mice also became less prone to the high blood sugar condition hyperglycaemia, which can lead to diabetes.

"The idea behind this research is that our circadian rhythms are coupled with metabolic processes and that can you modulate them pharmacologically," said lead scientist Professor Thomas Burris, from the Scripps Research Institute in Florida, US.

"As it turns out, the effect of that modulation is surprisingly positive - everything has been beneficial so far."

The injected compounds, known as SR9011 and SR9009, were administered to the animals twice a day for 12 days.

They targeted the hypothalamus, which houses the brain's "master clock" that controls circadian rhythms.

The drugs had an agonist effect, meaning they activated certain proteins. Two in particular were affected - REV-ERB alpha and REV-ERB beta, which play a key role in regulating circadian rhythms.

Obese mice lost weight despite being fed a diet high in fat and sugar.

Cholesterol levels in the blood of treated mice fell 47% while triglycerides - a harmful type of blood fat - were lowered by 12%.

A number of metabolism genes in the liver, skeletal muscle and fat tissue were also altered, causing the mice to burn up more energy.

However, the changes were not due to increased activity. In fact the animals displayed a 15% reduction in movement during the experiments.

Writing in an early online edition of the journal Nature, the scientists concluded: "Our observations that the REV-ERB agonists increase energy expenditure and decrease fat mass, plasma tricglycerides, and cholesterol levels, suggest that these compounds may be useful in the treatment of metabolic diseases."

 
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