Starving to avoid sleepiness, and cognitive impairments when sleep deprived

As anyone who has ever struggled to keep his or her eyes open after a big meal knows, eating can induce sleepiness. New research in fruit flies suggests that, conversely, being hungry may provide a way to stay awake without feeling groggy or mentally challenged.

Scientists at Washington University School of Medicine in St. Louis found in a study of fruit flies that starvation allows the need for nourishment to push aside the need for sleep. Like humans and rats, fruit flies cannot survive without sleep. But in a line of flies engineered to be sensitive to sleep deprivation, starvation nearly tripled the amount of time they could survive without sleep. The findings will be published next week in the online, open access journal PLoS Biology.

The researchers showed that the ability to resist the effects of sleep loss was linked to a protein that helps the fruit fly brain manage its storage and use of lipids, a class of molecules that includes fats such as cholesterol and fat-soluble vitamins such as vitamins A and D.

'The major drugs we have to either put people to sleep or keep them awake are all targeted to a small number of pathways in the brain, all of them having to do with neurotransmission,' says Paul Shaw, PhD, assistant professor of neurobiology and anatomy. 'Modifying lipid processing with drugs may provide us with a new way of tackling sleep problems that is more effective or has fewer side effects.'

The findings add a new wrinkle to the complex relationship between sleep and dietary metabolism. As well as the familiar post-prandial drowsiness, scientists also recognised about a decade ago that inadequate sleep results in obesity and contributes to the development of diabetes and coronary disease. Until now, no one had connected genes linked to lipid metabolism with regulation of the need for sleep.

Shaw and colleagues found that disabling a gene known as Lipid storage droplet 2 (Lsd2) in fruit flies produced effects similar to those of starvation, creating resistance to the urge to sleep and to the cognitive impairments normally created by sleeplessness. They are now working to identify the specific lipids affected by loss of Lsd2.