UCLA scientists have discovered that lean people experience a huge nighttime surge of ghrelin — the hormone that stimulates hunger — but obese people do not.
Scheduled for online publication on June 28 in the Proceedings of the National Academy of Sciences, the study suggests that obesity suppresses the ghrelin spike, perhaps disrupting the body's internal cues for hunger and overpowering its ability to regulate appetite. Ghrelin helps the body control its weight as part of a complex system that regulates food intake and energy output.
"We expected to find a different ghrelin pattern in obese people, but the big shock was that it happened at night," said Dr. Julio Licinio, professor of psychiatry and medicine at the David Geffen School of Medicine at UCLA. "At first glance, our findings appear contradictory. You'd expect the blood levels of the heavier men to contain more hunger hormone. Something must be overriding obese persons' ghrelin."
The team's findings may point to new targets for treating obesity, said Licinio, who also is a senior research scientist at the UCLA Neuropsychiatric Institute.
"It's possible that obese people have developed biological mechanisms that make them resistant to their own hormones," he said. "We must try to solve this mystery and explore new drugs to make them more sensitive to their bodies' internal cues."
Cells in the stomach secrete ghrelin into the blood, where it rises and falls in predictable daily patterns, spiking before meals when you are hungry and dropping after you eat.
Licinio's colleagues monitored ghrelin patterns in five lean men and five obese men every seven minutes for 24 hours. The team collected more than 200 blood samples per subject.
The scientists were surprised to discover a giant burst of ghrelin in the lean men's blood between midnight and 6 a.m. that surpassed pre-mealtime peaks of the hormone. Yet ghrelin levels remained flat in the obese men.
"The most powerful ghrelin surge was missing in the obese men, suggesting that their regulatory system has gone awry or is no longer able to listen to its own cues," Licinio said.
"This defies the stereotype of overweight people waking up in the middle of the night to raid the refrigerator," Licinio said. "The men in our study slept through the night, and both groups ate meals designed to maintain their current weight."
Licinio's team also monitored leptin and adiponectin, two hormones produced by the fat cells. Leptin signals fullness and cues a person to stop eating. Adiponectin helps regulate energy metabolism.
In addition to lower levels of ghrelin overall, the obese men showed higher levels of leptin and lower levels of adiponectin than the lean men. This confirmed earlier findings made by Licinio and other researchers.
"Again, this runs counter to common expectations," Licinio said. "You'd assume obese individuals would have lower levels of leptin, the fullness hormone, not higher."