Research subjects who slept only four hours a night for two nights had an 18 percent decrease in leptin, a hormone that tells the brain there is no need for more food, and a 28 percent increase in ghrelin, a hormone that triggers hunger.

The study volunteers, all healthy young men, reported a 24 percent increase in appetite, with a surge in desire for sweets, such as candy and cookies, salty foods such as chips and nuts, and starchy foods such as bread and pasta.

"This is the first study to show that sleep is a major regulator of these two hormones and to correlate the extent of the hormonal changes with the magnitude of the hunger change," said Eve Van Cauter, Ph.D., professor of medicine at the University of Chicago. "It provides biochemical evidence connecting the trend toward chronic sleep curtailment to obesity and its consequences, including metabolic syndrome and diabetes."

In the last 40 years, American adults have cut their average sleep time by nearly two hours. In 1960, U.S. adults slept an average of 8.5 hours a night. By 2002, that had fallen to less than seven hours a night. Over the same period, the proportion of young adults sleeping less than seven hours increased from 15.6 percent to 37.1 percent. Now, only 23.5 percent, or less than one out of four young adults, sleeps at least eight hours a night.

As sleep time fell, average weights rose. In 1960 only one out of four adults was overweight and about one out of nine was considered obese, with a body mass index of 30 or more. Now two out of three adults is overweight and nearly one out of three is obese.

Whether and how these two trends are connected, however, is unclear. Sleep-deprived rats eat more than those allowed normal sleep. Several epidemiologic studies showed that people who sleep less are more likely to be overweight. One recent study found that those who reported less than four hours of sleep a night were 73 percent more likely to be obese.

By providing the first data on the relationship between sleep and the hormones that regulate hunger, this study helps to confirm and begins to explain the connection.

Van Cauter and colleagues studied 12 healthy male volunteers in their early 20s to see how sleep loss affected the hormones that control appetite. Theses hormones -- ghrelin and leptin, both discovered in the last ten years -- represent the 'yin-yang' of appetite regulation. Ghrelin, made by the stomach, connotes hunger. Leptin, produced by fat cells, connotes satiety, telling the brain when we have eaten enough.

Van Cauter's team measured circulating levels of leptin and ghrelin before the study, after two nights of only four hours in bed (average sleep time 3 hours and 53 minutes) and after two nights of ten hours in bed (sleep time 9 hours and 8 minutes). They used questionnaires to assess hunger and the desire for different food types.

"We were particularly interested in the ratio of the two hormones," said Van Cauter, "the balance between ghrelin and leptin."

After a night with four hours of sleep, the ration of ghrelin to leptin increased by 71 percent compared to a night with ten hours in bed.

As hunger increased, food choices changed. After two nights of curtailed sleep the volunteers found foods such as candy, cookies and cake far more appealing. Desire for fruit, vegetables or dairy products increased much less.

"We don't yet know why food choice would shift," Van Cauter said. "Since the brain is fueled by glucose, we suspect it seeks simple carbohydrates when distressed by lack of sleep." At the same time, the added difficulty of making decisions while sleepy may weaken the motivation to select more nutritious foods, making it harder to push away the doughnuts in favor of a low-fat yoghurt.

"Our modern industrial society seems to have forgotten the importance of sleep," Van Cauter said. "We are all under pressure to perform, in school, at work, in social and professional settings, and tempted by multiple diversions. There is a sense that you can pack in more of life by skimping on sleep. But we are finding that people tend to replace reduced sleep with added calories, and that's not a healthy trade."

Modern scientific study of sleep began at the University of Chicago in 1953 with the discovery of REM sleep and subsequent studies that described the multiple stages of sleep. For many years, research on the consequences of sleep deprivation focused on the brain. Since 1999, however, the Van Cauter laboratory has published a series of studies describing the metabolic and hormonal consequences of chronic partial sleep loss – which is now common. Such studies include:

* A 1999 study showing that a significant sleep debt could trigger metabolic and endocrine changes that mimic many of the hallmarks of aging. * A 2000 paper that mapped out the stages of age-related sleep deterioration and showed how changes in sleep were mirrored by changes in hormone secretion, which in turn reduced sleep quality. * A 2001 study demonstrating that inadequate sleep could foster insulin-resistance, a risk factor for Type 2 diabetes. * A 2002 study showed that sleep deprivation could slow the response to vaccination, suggesting that sleep loss could reduce the ability to fight off an infection.

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The National Institutes of Health, the European Sleep Research Society, the Belgian Fonds de la Recherche Scientifique Medicale, the University of Chicago Diabetes Research and Training Grant and the University of Chicago Clinical Research Center funded this study. Authors include Esra Tasali and Plamen Penev of the University of Chicago and Karine Spiegel of the Universite Libre de Bruxelles, Belgium.