Microbiology/Genetics

The Gene of the Internal Clock Linked to Obesity

It impairs sugar and fat metabolism

By Stefan Anitei, Science Editor

15th of May 2007, 08:46 GMT

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Could the natural way of your sleep and how much you sleep influence the way you look?

It seems that they do, as researchers have discovered that a gene controlling the mammalian circadian clock seems to be implied in weight gain from fat-rich diets.

Researchers led by Joseph Besharse of the Medical College of Wisconsin and Carla Green of the University of Virginia found that when the clock gene Nocturnin was turned off in mice, the animals did not fatten even when put on a fat diet.

"We show evidence that the clock itself is behaving

correctly in the mutant mouse, but various aspects of lipid ands glucose metabolism are disrupted." said Besharse.

Nocturnin was discovered in the '90s by the same team and encodes for a protein synthesized in many tissues including the liver.

In daytime, the liver produces relatively low amounts of Nocturnin protein, but at night the synthesis boosts up to a hundredfold.

When the team knocked out the Nocturnin in mice and compared them to normal mice when put on the fat diets, the mice lacking Nocturnin displayed just minor weight gain, while normal mice achieved a double size compared to them.

Moreover, normal mice presented large stores of fat around their livers, while the mutants did not.

"They're better off without the gene, I guess, if you're just looking at obesity. However, the mutant mice have altered glucose metabolism on a standard diet. It is likely that the Nocturnin [protein], which is produced in multiple tissues-liver, fat cells, pancreas and gut-is affecting glucose and lipid metabolism at multiple levels. This triggers resistance to the hormone insulin secreted by the pancreas, which ferries glucose from the blood into individual cells, where it is converted to energy." said Besharse.

Insulin resistance is extremely dangerous in humans, triggering type 2 diabetes.

The team will continue to investigate Nocturnin's molecular mechanism in the liver, but also other organs, like eyes, brain and kidneys.

"Certainly it has crossed our minds that [a drug] that would inhibit the activity of Nocturnin might influence lipid [fat] storage." said Besharse.

TAGS:

gene | clock | internal | glucose | fat

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