Study Shows Our Appetite — and Obesity Risk — May Be Set in Infancy

Feeling peckish? Ghrelin, the body’s hunger hormone, could be to blame. But there’s something more subtle and harmful about the appetite booster than just prompting us to go back for seconds, according to new research published in the Journal of Clinical Investigation.

Researchers at the Saban Research Institute at Children’s Hospital Los Angeles (CHLA) examined ghrelin’s role in early brain development. They found that the hormone’s influence on long-term appetite development is linked to metabolic diseases such as obesity. The eye-opening discovery shows just how powerful hormonal signals can be, even during infancy.

How Does Ghrelin Work?

Ghrelin, produced in the gut, promotes appetite by interacting with cells in the hypothalamus, the area of the brain linked to appetite and the regulation of metabolism. It’s this abnormal communication between the gut and the brain, as this study shows, that’s linked to obesity, diabetes, and heart disease.

Although ghrelin is one of the most powerful appetite stimulating chemicals we know of, scientists didn’t understand much about the role of neonatal ghrelin before this study, said lead investigator Sebastien G. Bouret, Ph.D., of CHLA and associate professor at the Keck School of Medicine at the University of Southern California.


Researchers still don’t know how to repair this gut-brain miscommunication, but Bouret says that understanding this interaction will be crucial for future research.

Researchers conducted two experiments on mice to study the influence of ghrelin during early life. When scientists blocked ghrelin during early infant development, the mice suffered from lifelong metabolic conditions, including obesity and diabetes. Surprisingly, increasing ghrelin levels during this developmental period also caused metabolic dysfunction. The results highlight the need to focus specifically on metabolic disruption in babies and young children.

“We were very surprised when we first saw that blocking neonatal ghrelin causes obesity and hyperphagia (excessive hunger),” Bouret said. “What our study tells us is that, in pediatric developmental research, one cannot make a conclusion based on what is known in adults. Often, hormones exert distinct roles during development.”

Curbing Metabolic Disease

Several groups of people may be particularly susceptible to the negative effects of ghrelin, Bouret said. One is people with Prader-Willi syndrome (PWS), a genetic disease characterized by insatiable appetite and morbid obesity. Bouret said that excess ghrelin is a hallmark of adults suffering from PWS, and that these elevated levels crop up as early as infancy — before the development of obesity.

In pediatric developmental research, one cannot make a conclusion based on what is known in adults. Often, hormones exert distinct roles during development.
Sebastien G. Bouret, Ph.D., Children’s Hospital Los Angeles

“It is therefore possible that these abnormally high levels of ghrelin found in PWS babies might affect hypothalamic development and contribute to the development of obesity and hyperphagia,” Bouret said. “This is actually a line of research that we are currently doing in collaboration with the Foundation for Prader-Willi Research.”

Another group of people who could be susceptible to the negative effects of ghrelin are obese and overweight children.

“Epidemiological data have suggested that excess nutrition and growth during pre- and/or postnatal life may contribute to the etiology of obesity and related diseases later in life,” Bouret said. He added that ghrelin is the ideal hormone for transmitting signals from the gut to the developing brain in response to changes in the amount and type of foods we eat.

Clearly, efforts to curb metabolic disease must start at an early age.

“Our data illustrate the importance of the timing of the intervention, and also show the importance of performing pediatric developmental research to design efficient strategies to cure childhood obesity,” Bouret said.