Why starved flies need less sleep

Low lipid levels keep insects buzzing, a new study finds

Eating may rejuvenate a tired body, but new research in fruit flies suggests that fasting actually helps ward off the ravages of sleep deprivation.

Starving sleep-deprived fruit flies sheltered the insects from sleepiness and fended off learning and memory difficulties associated with grogginess, researchers report August 31 in PLoS Biology. Starvation may slow down the buildup of sleep-inducing substances that accumulate while an animal is awake, says Paul Shaw, a neuroscientist at Washington University School of Medicine in St. Louis who led the work.

The new study suggests that a rise in lipids, a type of fat, during wakefulness makes fruit flies sluggish. Learning how lipids induce sleepiness may eventually help develop new sleep remedies and shed new light on how sleep evolved.

The findings herald “a big change for the field” of sleep research, says Robert Greene, a neurobiologist at the University of Texas Southwestern Medical Center at Dallas. “It emphasizes the importance of metabolism and its interaction with sleep.”

Scientists are still debating why animals and people sleep (SN: 10/24/09, p. 16). To learn what happens during sleep, most researchers compare sleep-deprived animals with animals that have been allowed to sleep normally. In the new study, Shaw’s team took a different approach. The researchers wanted to see if there was a difference between fruit flies that have been kept up all night by bumping them awake whenever they tried to sleep and fruit flies that stay awake longer than normal because they are starving.

Fruit flies that are up and around because they are starving stay alert and active and have no trouble with learning to avoid a noxious substance, the team found. That contrasts with well-fed, but sleep-deprived fruit flies, which do have learning and memory problems. Starved fruit flies also don’t need to make up for lost sleep the way sleep-deprived flies do.

It makes sense for starving animals to stay alert. “Starvation happens all the time in the wild, and if you don’t have food, you’d better be out trying to find it,” Shaw says. If a starving animal builds up a sleep-inducing substance at the normal rate, it risks becoming someone else’s food.

Shaw’s study “looks at sleep in a different way, which I think is right on the mark,” says Jerome Siegel, a neuroscientist at the University of California, Los Angeles. “It looks at sleep’s role in an animal’s overall survival rather than just for some specific physiological process.”

Shaw and his team traced the source of sleepiness in sleep-deprived flies to lipids. Fruit flies with mutations in a biological clock gene called cycle have higher than normal levels of triglycerides, a type of lipid. These mutant flies are also very sensitive to sleep deprivation, and begin to die if kept awake for more than 10 hours past their normal bedtime. But starvation allows the flies to stay up for 28 hours past bedtime.

The researchers found that blocking the breakdown of triglycerides for energy in the starving cycle mutant fruit flies caused the insects to need recovery sleep. That indicates that lipids may be the substance that builds up and makes flies sleepy.

Fruit flies with mutations in a gene called brummer also have high lipid levels. Those flies need to sleep a lot to recover from sleep deprivation, but starvation reduces the need for recovery sleep. Fruit flies with a mutation in the Lipid storage droplet 2 (Lsd2) gene are lean and have low lipid levels. Those flies don’t get sleepy, as measured by a biomarker for sleepiness, and don’t need recovery sleep when sleep deprived, the team found.

Taken together, Shaw says the findings indicate that lipids may act to change the activity of neurons in the brain and cause fruit flies to get sleepy the longer they are awake. Starvation burns off excess lipids, slowing down the rate at which fruit flies get sleepy. Of course, even starving fruit flies do eventually start to get sleepy, and animals can’t live long without food. “It won’t work forever,” Shaw says.

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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