Appetite (and Genes) May Drive Early Weight Gain

Ricki Lewis, PhD

February 20, 2014

Genetics may influence appetite and eating behavior in young children in ways that lead to accelerated weight gain that can, in turn, lead to obesity, according to results from 2 studies published online February 17 in JAMA Pediatrics.

Traditional tools to assess polygenic traits (family, adoption, and twin studies) identify heritability greater than 50% for body weight. Two overlapping groups of researchers from University College London and King's College London, United Kingdom, have conducted studies that tease out possible genetic mechanisms behind early weight gain.

Since 2008, several studies have associated hearty appetite with higher body mass index. Specifically, those at risk have higher than average food responsiveness (FR) coupled with lower than average satiety responsiveness (SR).

FR is the degree to which food cues (smell or appearance) compel eating behavior and reflects neural reward pathways in the brain. SR is the feeling of fullness and satisfaction after eating and reflects neuroendocrine feedback loops involving hormonal satiety factors that interact with receptors in the brain. Differences in satiety are thought to underlie some of the inherited differences seen in how soon individuals stop eating.

In the first study, Cornelia H. M. van Jaarsveld, PhD, a research fellow at King's College London, and colleagues, examined appetite and weight gain in same-sex, nonidentical twin pairs during the first 15 months of life. The design removed the confounding effects of differences in eating behavior among families.

The researchers assessed FR and SR using the Baby Eating Behavior Questionnaire among 800 twin pairs born between March 1, 2007, and December 15, 2007, assessing weight an average of 11.5 times for the first 15 months. Discordance was defined as a within-pair difference of at least 1 standard deviation unit.

Of the 800 twin pairs, 172 pairs were discordant for SR and 121 pairs for FR. Although there was no difference in weight at birth among discordant pairs, the infants with higher FR and lower SR grew faster than their siblings.

At 6 months of age, babies with higher FR were an average of 654 g (95% confidence interval [CI], 395 - 913 g) heavier, and at 15 months, they were an average of 991 g (95% CI, 484 - 1498 g) heavier, than their siblings. For twins discordant for SR, weights differed by a mean of 637 g (95% CI, 438 - 836 g) at 6 months and a mean of 918 g (95% CI, 569 - 1267 g) at 15 months.

Considering that mean weight at 15 months is 10.3 kg, the finding that the twins at opposite extremes differed by nearly a kilogram is significant. The investigators conclude that the study "corroborates the hypothesis that a hearty appetite in infancy is a risk factor for faster weight gain."

Limitations of the study include the effects of small differences in birth weight and body length and the parental source of the data.

Low Satiety a Risk

In the second study, Clare H. Llewellyn, PhD, a research associate at King's College London, and coworkers focused on low satiety responsiveness as a genetic risk factor for obesity in children. They used a cross-sectional observational design on twins born between 1994 and 1996, selecting 2258 unrelated children, 1 from each pair. The participants had previously participated in 2 studies that gathered data on appetite and weight, and on genotype.

The researchers derived a polygenic risk score (PRS) based on single nucleotide polymorphisms in 28 obesity-related genes from a meta-analysis of genome-wide association study findings. The study looked for associations among single nucleotide polymorphisms patterns; satiety responsiveness that parents assessed, using a rating scale; and anthropometric measures (body mass index and waist circumference).

These results suggest that inability to feel full soon after eating is genetically influenced. The gene variants were associated negatively with satiety responsiveness (β coefficient, −0.060; 95% CI, −0.019 to −0.101) and positively with adiposity (β coefficient, 0.177 [95% CI, 0.136 - 0.218] for body mass index standard deviation; β coefficient, 0.167 [95% CI, 0.126 - 0.208] for waist standard deviation scores). More children in the top quartile of the PRS were overweight than in the lowest quartile (18.5% vs 7.2%; odds ratio, 2.90 [95% CI, 1.98 - 4.25]).

Limitations of the study include an inability to determine causality, the fact that weight among twins may not represent the general population, and the fact that parents obtained the measurements. The researchers conclude that their results support the hypothesis that the appetite regulatory system is one way that gene variants influence adiposity.

Lifestyle Factors Contribute

In an accompanying editorial, Daniel W. Belsky, PhD, from the Center for the Study of Aging and Human Development at the Duke University Medical Center, Durham, North Carolina, discusses the pervasive and persistent "obesogenic environment" that many children face. Because the availability of food is constant, he argues, genetic factors may explain differences in weight gain patterns.

"The link between appetite and polygenic risk for obesity suggests that children identified in this way may be responsive to preventive interventions that promote healthy lifestyle practices; observational studies indicate that polygenic risk for obesity is amplified by poor diet and can be mitigated by active lifestyle," the editorial concludes.

The investigators and commentator have disclosed no relevant financial relationships.

JAMA Pediatr. Published online February 17, 2014. van Jaarsveld abstract, Llewellyn abstract, Editorial extract


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