Ghrelin Hunger Hormone Poses Obesity Risk For Life When Imbalanced In Infants

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An imbalance of the hunger hormone ghrelin in infancy could pose lifelong risks for obesity. Kona Gallagher, CC BY-SA 2.0

Unstable levels of the hunger hormone ghrelin in infancy may pose lifelong risks for obesity, a new study finds. The results suggest a departure from the will power-focused ideas of the past, where obesity is a simple and direct result of eating right and exercising often.

The sensation of feeling hungry is no accident. In mammals, the stomach produces ghrelin, a key hormone that tells the brain nutrient stores are low and that the body needs food. Sometimes the system goes haywire. People with Prader-Willi syndrome, for instance, never lose their hunger because their bodies produce too much ghrelin. Now research argues a portion of obese adults may experience the same effects, based solely on how much ghrelin their bodies produced as babies.

"We've shown that neonatal ghrelin directly influences development in the part of the brain related to appetite and the regulation of metabolism," said principal investigator Dr. Sebastien G. Bouret, of the Developmental Neuroscience Program at the Children’s Hospital of Los Angeles, in a statement.

The U.S. is no stranger to obesity. By the latest estimates, more than one-third of the country (34.9 percent or 78.6 million people) are obese, resulting in annual medical costs of approximately $147 billion. On an individual level, the risks are great. Obesity predisposes people to developing type 2 diabetes, heart disease, hypertension, and high cholesterol, all of which put them at a greater risk for early death.

The latest study tried to assess how much those risks went up when infants’ ghrelin levels threw off their normal path for brain development. Scientists turned to mouse models, homing in on the hypothalamus — a brain region responsible for receiving ghrelin signals and, through gastric acid secretion, prepping the stomach for food intake. Inside the hypothalamus is a dense collection of neurons known as the arcuate nucleus. Here the team measured ghrelin’s effects directly, via axonal projections.

In two different experiments, the research team checked ghrelin’s influence. The first involved blocking the hormone soon after birth, which caused more axonal projections and a slew of metabolic dysfunctions. The second experiment did the opposite: When the team revved up ghrelin production, axonal projections quieted and other metabolic dysfunction cropped up. Both outcomes seemed to reflect the need for balance in a child’s early years.

"Our study underlines the importance of maintaining a healthy hormonal balance — including ghrelin — during early life, to ensure proper development of brain-feeding centers," Bouret said.

There are several ways parents can help give their kids a head start in maintaining healthy ghrelin levels, and much of the advice applies not just to developing infants, but to the general public. They can start by putting their infants to bed as often as necessary and not skimping on naptime. One 2008 study showed one night of sleep deprivation raised people’s ghrelin levels. Though, that doesn’t bode well for the parents on particularly cry-heavy nights.

Another way is to keep a healthier diet. High-fat foods have been shown to keep ghrelin levels low for a far shorter time than carbohydrate- or protein-based meals. That’s why fasting often precedes a big binge: Ghrelin levels are at their peak right before a meal and after a long period without food. Depriving the body is stressful and generally only leads to greater consumption later, which slows the metabolism.

All this contributes to obesity later in life. If the risks can be minimized before children begin to express them, the nation as a whole has no choice but to get healthier. “A better understanding of the relationship between ghrelin levels early in life and the development of disorders such as Prader-Willi syndrome or childhood obesity,” Bouret concluded, “will be crucial as we seek to develop interventional studies to treat and, hopefully, reverse symptoms of metabolic diseases.”

Source: Steculorum S, Collden G, Coupe B, et al. Neonatal ghrelin programs development of hypothalamic feeding circuits. Journal of Clinical Investigation. 2015.

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