Why narcoleptics get fat

Now researchers reporting in the October issue of Cell Metabolism, a Cell Press publication, appear to have an answer as to why. It seems a deficiency of the neuropeptide hormone orexin, an ingredient that encourages hunger and wakefulness, may leave them with a lack of energy-burning brown fat.

The findings may lead to orexin-based weight loss therapies for those with narcolepsy and for the rest of us, too, according to the researchers.

Orexins are rather unique in that they allow one to eat more and lose more at the same time, explained Devanjan Sikder of the Sanford-Burnham Research Institute. "It is a couch potato's dream."

Fat comes in one of two types: white or brown. White fat stores calories while brown fat burns them, generating heat in the process. There had been hints that orexins might influence body temperature, but it wasn't clear exactly how.

The new evidence in mice shows that orexins are critical for the formation of mature brown fat from its precursors. With too little orexin, animals' brown fat activity drops along with their energy expenditure. Likewise, mice injected with orexin show a substantial loss of fat.

The findings bolster the emerging concept that those with less active brown fat may be destined from birth, or even before, to be fatter. "They are somehow predisposed," Sikder said.

There are already ways of stimulating brown fat's production, but it isn't easy to do. For instance, more brown fat is produced when you spend a lot of time in the cold. The new findings suggest that orexin therapies might be useful for increasing brown fat and literally melting extra calories away.

"One caveat is that orexin might increase arousal," the researchers wrote, "although this is expected only under sleep deprived conditions."

Sikder says it will now also be worthwhile to examine orexin-deficient people with narcolepsy to find out whether their brown fat activity is indeed compromised.