The hormone orexin activates the hypoxia-inducible factor 1 (HIF-1), which has long been known to stimulate cancerous tumor growth. Researchers made the discovery while investigating how orexin might control sleep and hunger. The lack of orexin has been shown, in previous research, to cause narcolepsy.

Researchers at the University of Texas Southwestern Medical Center, Dallas, used a massive gene-screening technique to identify genes that orexin either turned on or inhibited. They found that HIF1-alpha was among the most highly activated of any gene in the study. And when orexin stimulated HIF1-alpha, it in turn increased the expression of a variety of genes dedicated to burning sugar to provide energy for the body.

The authors note that the findings help explain orexin's link to the metabolic system, hypothesizing that when a body has low blood sugar and gets hungry, the increase in orexin activates HIF-1 production, revving up metabolism so the body gets the most energy out of the sugar on hand.

"This orexin pathway we found is basically an overdrive function. Even though blood sugar levels are low, you're not only awake, but you're also energetic because of the action of HIF-1," said Thomas Kodadek, PhD, chief of translational research at UT Southwestern and senior author of the study. "In retrospect, our findings make a lot of sense, but they were surprising at the time."

He added that not only was this orexin-HIF link unexpected, but it showed an entirely new way HIF-1 operates. There have been a few recent studies on its function in healthy tissues, but none involving mechanisms related to sleep, he said.

Next up, the researchers plan to genetically engineer mice that lack HIF-1 in the brain in order to determine the effects on wakefulness and activity levels of the animals. They also plan to further study how orexin and oxygen levels interact to control energy metabolism in cells. The research, "The Neurohormone Orexin Stimulates Hypoxia-Inducible Factor-1 Activity", appears in the online version of the journal Genes and Development.