Satiety sensitivity may explain predisposition to childhood obesity

Common obesity risk genes influence adiposity by way of appetite mechanisms, explaining how environments and genes lead to weight gain among pediatrics, according to data from two studies published simultaneously in JAMA Pediatrics today.

“Obesity is a major issue in child health,” Jane Wardle, PhD, a researcher for both studies, said in a press release. “Identifying factors that promote or protect against weight gain could help identify targets for obesity intervention and prevention in future. These findings are extremely powerful because we were comparing children of the same age and same sex growing up in the same family in order to reveal the role that appetite plays in infant growth.”

Sibling analysis on appetite

In one of the studies, van Jaarsveld and colleagues from the University College London (UCL) Health Behaviour Research Centre analyzed 172 same-sex twin pairs from birth to 15 months. The pairs were discordant for satiety responsiveness and 121 pairs were discordant for food responsiveness. Within-pair analyses demonstrated those with greater food responsiveness and those with lower satiety responsiveness grew more than their sibling.

At age 6 months, patients with higher food responsiveness were 654 g heavier (95% CI, 395-913); at age 15 months, they were 991 g heavier (95% CI, 484-1,498), according to data.

The weight differences between siblings in the satiety responsiveness group were 637 g (95% CI, 438-836) at age 6 months and 918 g (95% CI, 569-1,267) at age 15 months, researchers wrote.

“It might make life easy to have a baby with a hearty appetite, but as she grows up, parents may need to be alert for tendencies to be somewhat over-responsive to food cues in the environment, or somewhat unresponsive to fullness. This behavior could put her at risk of gaining weight faster than is good for her,” Wardle said.

Mechanisms in genetic risk

In a related study, Clare H. Llewellyn, PhD, of the UCL Health Behaviour Research Centre, and colleagues conducted a cross-sectional observation of a population-based cohort of twins born from 1994 to 1996, including 2,258 unrelated children (53.3% female; mean age, 9.9 years).

To evaluate whether satiety responsiveness is an intermediate behavioral phenotype associated with genetic predisposition to obesity in youths, researchers created a polygenic risk score (PRS) that involved 28 common obesity-related single nucleotide polymorphisms.

“As expected, we found that children with a higher PRS (more obesity-risk genetic variants) were likely to have larger BMI and waist circumference,” Llewellyn said in a press release. “But more importantly, we also found that these children were more likely to have low satiety responsiveness.”

The PRS was negatively related to satiety responsiveness (beta coefficient, –0.06; 95% CI, –0.019 to –0.101) and positively related to adiposity (beta coefficient, 0.177; 95% CI, 0.136-0.218 for BMI; beta coefficient, 0.167; 95% CI, 0.126-0.208 for waist), according to data.

Moreover, children in the top 25% of the risk score were overweight compared with the lowest 25% (18.5% vs. 7.2%; OR=2.9; 95% CI, 1.98-4.25). In addition, the link between the risk score and adiposity indicated a significant response to satiety (P=.006 for BMI; P=.005 for waist). These data suggest that satiety sensitivity could be targeted for interventions, according to Llewellyn.

“For example, children with lower satiety sensitivity could be taught techniques that might improve their fullness signals when eating, such as slowing their eating speed. Another approach might be to provide better advice to parents and children about appropriate portion sizes, limiting access to ‘second helpings’ and ensuring tempting treats are out of sight between meals,” Llewellyn said in the release.

The obesogenic ‘puzzle’

In an accompanying editorial, Daniel W. Belsky, PhD, of the Center for the Study of Aging and Human Development at Duke University Medical Center, wrote that solving the obesogenic “puzzle” is an ongoing public health priority.

“In suggesting infant and early childhood satiety responsiveness as a mediator of polygenic risk for obesity, these studies highlight an important translational application of genetic discoveries: To identify intermediate phenotypes in disease pathogenesis to serve as targets for intervention and/or provide guidance as to when in development and with whom to intervene,” he wrote. “Findings suggest that a mother’s report of her child’s appetite may be informative in identifying children especially vulnerable to developing obesity.”

For more information:

Belsky DW. JAMA Pediatr. 2014;doi:10.1001/jamapediatrics.2013.5291.

Llewellyn CH. JAMA Pediatr. 2014;doi:10.1001/jamapediatrics.2013.4944.

van Jaarsveld CHM. JAMA Pediatr. 2014;doi:10.1001/jamapediatrics.2013.4951.

Disclosure: The researchers report no relevant financial disclosures.